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    Clinical Trial Results:
    A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of MK-8228 (Letermovir) Versus Valganciclovir for the Prevention of Human Cytomegalovirus (CMV) Disease in Adult Kidney Transplant Recipients

    Summary
    EudraCT number
    		 2017-001055-30
    Trial protocol
    		 ES   AT   FR   HU   GB   BE   PL   IT  
    Global end of trial date
    05 Apr 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Apr 2023
    First version publication date
    14 Apr 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    8228-002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03443869
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Merck: MK-8228-002
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme LLC
    Sponsor organisation address
    126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    05 Apr 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Apr 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Apr 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to evaluate the efficacy of letermovir (LET) versus valganciclovir (VGCV) in preventing CMV disease in adult kidney transplant recipients. The primary hypotheses are that LET is non-inferior to VGCV; and if non-inferiority is demonstrated, that LET is superior to VGCV, in preventing CMV disease through 52 weeks post-transplant.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 May 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 24
    Country: Number of subjects enrolled
    Australia: 35
    Country: Number of subjects enrolled
    Austria: 15
    Country: Number of subjects enrolled
    Belgium: 28
    Country: Number of subjects enrolled
    Canada: 41
    Country: Number of subjects enrolled
    Colombia: 4
    Country: Number of subjects enrolled
    France: 40
    Country: Number of subjects enrolled
    Germany: 45
    Country: Number of subjects enrolled
    Hungary: 17
    Country: Number of subjects enrolled
    Italy: 20
    Country: Number of subjects enrolled
    Mexico: 32
    Country: Number of subjects enrolled
    New Zealand: 10
    Country: Number of subjects enrolled
    Poland: 5
    Country: Number of subjects enrolled
    Spain: 42
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    United States: 241
    Worldwide total number of subjects
    601
    EEA total number of subjects
    212
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    495
    From 65 to 84 years
    106
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Male/Female participants of at least 18 years of age with receipt of a kidney transplant were enrolled in this trial.

    Period 1
    Period 1 title
    Overall (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Letermovir
    Arm description
    		 LET 480 mg (or 240 mg when administered concomitantly with cyclosporin A) tablet orally; placebo to VGCV tablet orally once daily; and 400-mg capsule of acyclovir (ACV) orally every 12 hours for 28 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Letermovir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    480 mg (or 240 mg when co-administered with cyclosporin A) once daily for 28 weeks

    Investigational medicinal product name
    Placebo to VGCV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Once daily for 28 weeks

    Investigational medicinal product name
    Acyclovir (ACV)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400 mg every 12 hours for 28 weeks

    Arm title
    		 Valganciclovir
    Arm description
    		 900 mg VGCV tablet orally, once daily; placebo to LET tablet orally once daily; and placebo to ACV orally every 12 hours for 28 weeks
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Valganciclovir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    900 mg once daily for 28 weeks

    Investigational medicinal product name
    Placebo to LET
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Once daily for 28 weeks

    Investigational medicinal product name
    Placebo to ACV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Every 12 hours for 28 weeks

    Number of subjects in period 1
    		Letermovir Valganciclovir
    Started
    301
    300
    Treated
    292
    297
    Completed
    256
    266
    Not completed
    45
    34
         Consent withdrawn by subject
    34
    22
         Physician decision
    3
    3
         Death
    3
    3
         Unknown
    4
    4
         Lost to follow-up
    1
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Letermovir
    Reporting group description
    		 LET 480 mg (or 240 mg when administered concomitantly with cyclosporin A) tablet orally; placebo to VGCV tablet orally once daily; and 400-mg capsule of acyclovir (ACV) orally every 12 hours for 28 weeks

    Reporting group title
    Valganciclovir
    Reporting group description
    		 900 mg VGCV tablet orally, once daily; placebo to LET tablet orally once daily; and placebo to ACV orally every 12 hours for 28 weeks

    Reporting group values
    		 Letermovir Valganciclovir Total
    Number of subjects
    		 301 300 601
    Age Categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 49.6 ( 14.8 ) 49.5 ( 15.1 ) -
    Gender Categorical
    Units: Participants
        Female
    		 84 90 174
        Male
    		 217 210 427
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 3 4 7
        Asian
    		 5 10 15
        Black or African American
    		 22 33 55
        Multiple
    		 9 6 15
        White
    		 259 246 505
        Missing
    		 3 1 4
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 56 45 101
        Not Hispanic or Latino
    		 230 240 470
        Not Reported
    		 6 9 15
        Unknown
    		 5 4 9
        Missing
    		 4 2 6

    End points

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    End points reporting groups
    Reporting group title
    Letermovir
    Reporting group description
    		 LET 480 mg (or 240 mg when administered concomitantly with cyclosporin A) tablet orally; placebo to VGCV tablet orally once daily; and 400-mg capsule of acyclovir (ACV) orally every 12 hours for 28 weeks

    Reporting group title
    Valganciclovir
    Reporting group description
    		 900 mg VGCV tablet orally, once daily; placebo to LET tablet orally once daily; and placebo to ACV orally every 12 hours for 28 weeks

    Primary: Percentage of Participants with Adjudicated CMV Disease Through 52 weeks Post-transplant

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    End point title
    		 Percentage of Participants with Adjudicated CMV Disease Through 52 weeks Post-transplant
    End point description
    CMV disease was defined as the presence of either CMV end-organ disease or CMV syndrome and was confirmed by an independent, blinded Clinical Adjudication Committee (CAC). Only CAC-confirmed (“adjudicated”) cases were included in percentage of participants who met the endpoint. Investigator-assessed cases which were not confirmed by the CAC were not included. Analysis population consisted of all randomized participants who received at least one dose of study treatment, were CMV seropositive organ donor/CMV seronegative organ recipient (D+/R-), and had no detectable CMV viral DNA (measured by central laboratory) on Day 1.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Letermovir Valganciclovir
    Number of subjects analysed
    289
    297
    Units: Percentage of Participants
        number (not applicable)
    10.4
    11.8
    Statistical analysis title
    		 LET vs VGCV
    Statistical analysis description
    The Observed failure (OF) approach was used to handle missing values, that is participants who had discontinued prematurely from the study for any reason were not considered failures
    Comparison groups
    Valganciclovir v Letermovir
    Number of subjects included in analysis
    586
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 Stratum-adjusted Treatment Difference
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.5
         upper limit
    		 3.8
    Notes
    [1] - LET was concluded non-inferior to VGCV if the upper bound of the two-sided 95% CI for difference in percentage of participants with adjudicated CMV disease (LET – VGCV) was no higher than 10%

    Secondary: Percentage of Participants with Adjudicated CMV Disease Through 28 weeks Post-transplant

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    End point title
    		 Percentage of Participants with Adjudicated CMV Disease Through 28 weeks Post-transplant
    End point description
    CMV disease was defined as the presence of either CMV end-organ disease or CMV syndrome and was confirmed by an independent, blinded CAC. Only CAC-confirmed (“adjudicated”) cases were included in percentage of participants who met the endpoint. Investigator-assessed cases which were not confirmed by the CAC were not included. Analysis population consisted of all randomized participants who received at least one dose of study treatment, were CMV D+/R-, and had no detectable CMV viral DNA (measured by central laboratory) on Day 1.
    End point type
    Secondary
    End point timeframe
    Up to 28 weeks
    End point values
    		 Letermovir Valganciclovir
    Number of subjects analysed
    289
    297
    Units: Percentage of Participants
        number (not applicable)
    0.0
    1.7
    Statistical analysis title
    		 LET vs VGCV
    Statistical analysis description
    The Observed failure (OF) approach was used to handle missing values, that is participants who had discontinued prematurely from the study for any reason were not considered failures
    Comparison groups
    Letermovir v Valganciclovir
    Number of subjects included in analysis
    586
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Stratum-adjusted Treatment Difference
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 0.1

    Secondary: Time to Onset of Adjudicated CMV Disease through 52 weeks Post-transplant

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    End point title
    		 Time to Onset of Adjudicated CMV Disease through 52 weeks Post-transplant
    End point description
    The time to onset of adjudicated CMV disease was calculated in days, from the day of randomization to the day of onset of CMV disease as determined by the CAC. Note: 9999 indicated that the median time to event was not reached as fewer than half the participants reached this endpoint. Analysis population consisted of all randomized participants who received at least one dose of study treatment, were CMV D+/R-, and had no detectable CMV viral DNA (measured by central laboratory) on Day 1.
    End point type
    Secondary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Letermovir Valganciclovir
    Number of subjects analysed
    289
    297
    Units: Days
        median (confidence interval 95%)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with any AE

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    End point title
    		 Percentage of Participants with any AE
    End point description
    An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants who experienced 1 or more AEs was reported. Analysis performed for all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Letermovir Valganciclovir
    Number of subjects analysed
    292
    297
    Units: Percentage of Particpants
        number (not applicable)
    92.8
    92.9
    Statistical analysis title
    		 LET vs VLGV
    Comparison groups
    Letermovir v Valganciclovir
    Number of subjects included in analysis
    589
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.4
         upper limit
    		 4.2

    Secondary: Percentage of Participants with any Drug-related Serious Adverse Event (SAE)

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    End point title
    		 Percentage of Participants with any Drug-related Serious Adverse Event (SAE)
    End point description
    An SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. SAEs that the investigator determined the relationship of the AE to the treatment as at least possibly related were reported. Analysis performed for all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Letermovir Valganciclovir
    Number of subjects analysed
    292
    297
    Units: Percentage of Participants
        number (not applicable)
    1.4
    5.1
    Statistical analysis title
    		 LET vs VLGV
    Comparison groups
    Letermovir v Valganciclovir
    Number of subjects included in analysis
    589
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    -3.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 -0.9

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 52 weeks
    Adverse event reporting additional description
    All-Cause Mortality included all randomized participants. Non-serious and SAEs were reported for all randomized participants who received at least one dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Letermovir
    Reporting group description
    		 LET 480 mg (or 240 mg when administered concomitantly with cyclosporin A) tablet orally; placebo to VGCV tablet orally once daily; and 400-mg capsule of ACV orally every 12 hours for 28 weeks

    Reporting group title
    Valganciclovir
    Reporting group description
    		 900 mg VGCV tablet orally, once daily; placebo to LET tablet orally once daily; and placebo to ACV orally every 12 hours for 28 weeks

    Serious adverse events
    		 Letermovir Valganciclovir
    Total subjects affected by serious adverse events
         subjects affected / exposed
    118 / 292 (40.41%)
    129 / 297 (43.43%)
         number of deaths (all causes)
    5
    3
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ocular lymphoma
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post transplant lymphoproliferative disorder
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign renal neoplasm
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Extremity necrosis
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    4 / 292 (1.37%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 292 (0.00%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 292 (0.34%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery stenosis
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    8 / 292 (2.74%)
    5 / 297 (1.68%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Puncture site pain
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malacoplakia
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implant site necrosis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implant site extravasation
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Discomfort
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehiscence
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    9 / 292 (3.08%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Transplant rejection
         subjects affected / exposed
    6 / 292 (2.05%)
    9 / 297 (3.03%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney transplant rejection
         subjects affected / exposed
    5 / 292 (1.71%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumomediastinum
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    3 / 292 (1.03%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    7 / 292 (2.40%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    0 / 292 (0.00%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Complications of transplanted kidney
         subjects affected / exposed
    3 / 292 (1.03%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delayed graft function
         subjects affected / exposed
    2 / 292 (0.68%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scapula fracture
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft haemorrhage
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site discharge
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site erythema
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site pain
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural urine leak
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative ileus
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal lymphocele
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal transplant failure
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft complication
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous haematoma
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transplant failure
         subjects affected / exposed
    1 / 292 (0.34%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral injury
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 292 (0.00%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shunt thrombosis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    4 / 292 (1.37%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 292 (0.00%)
    4 / 297 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    1 / 292 (0.34%)
    5 / 297 (1.68%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    2 / 292 (0.68%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sickle cell anaemia with crisis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    4 / 292 (1.37%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    2 / 4
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoplastic anaemia
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    2 / 292 (0.68%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    2 / 292 (0.68%)
    9 / 297 (3.03%)
         occurrences causally related to treatment / all
    2 / 2
    6 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Incarcerated inguinal hernia
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    2 / 292 (0.68%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gingivitis ulcerative
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 292 (0.68%)
    8 / 297 (2.69%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall haematoma
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 292 (0.00%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overflow diarrhoea
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    8 / 292 (2.74%)
    9 / 297 (3.03%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcapsular renal haematoma
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    End stage renal disease
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Focal segmental glomerulosclerosis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    IgA nephropathy
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy toxic
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelocaliectasis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal artery stenosis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst haemorrhage
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal haematoma
         subjects affected / exposed
    1 / 292 (0.34%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 292 (0.34%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder tamponade
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    0 / 292 (0.00%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    2 / 292 (0.68%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinoma
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glomerulonephritis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Musculoskeletal and connective tissue disorders
    Spinal pain
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial pyelonephritis
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenovirus infection
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall abscess
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal sepsis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Campylobacter gastroenteritis
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronavirus infection
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus colitis
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus gastritis
         subjects affected / exposed
    2 / 292 (0.68%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus hepatitis
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    7 / 292 (2.40%)
    8 / 297 (2.69%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus syndrome
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus viraemia
         subjects affected / exposed
    2 / 292 (0.68%)
    4 / 297 (1.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epstein-Barr virus infection
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected urinoma
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney infection
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymph node tuberculosis
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Norovirus infection
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parvovirus B19 infection
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parvovirus infection
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Penile gangrene
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 292 (0.34%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia cytomegaloviral
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia klebsiella
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia parainfluenzae viral
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyomavirus-associated nephropathy
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 292 (0.34%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection enterococcal
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection pseudomonal
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    4 / 292 (1.37%)
    4 / 297 (1.35%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    4 / 292 (1.37%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal graft infection
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 292 (0.00%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    8 / 292 (2.74%)
    8 / 297 (2.69%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 292 (0.34%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    2 / 292 (0.68%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 292 (0.34%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    2 / 292 (0.68%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 292 (0.34%)
    3 / 297 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperlipidaemia
         subjects affected / exposed
    1 / 292 (0.34%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypervolaemia
         subjects affected / exposed
    2 / 292 (0.68%)
    0 / 297 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    1 / 292 (0.34%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    New onset diabetes after transplantation
         subjects affected / exposed
    3 / 292 (1.03%)
    2 / 297 (0.67%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 292 (0.00%)
    1 / 297 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Letermovir Valganciclovir
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    239 / 292 (81.85%)
    243 / 297 (81.82%)
    Investigations
    White blood cell count decreased
         subjects affected / exposed
    3 / 292 (1.03%)
    15 / 297 (5.05%)
         occurrences all number
    4
    20
    Blood creatinine increased
         subjects affected / exposed
    26 / 292 (8.90%)
    39 / 297 (13.13%)
         occurrences all number
    29
    46
    Injury, poisoning and procedural complications
    Procedural pain
         subjects affected / exposed
    8 / 292 (2.74%)
    19 / 297 (6.40%)
         occurrences all number
    9
    22
    Vascular disorders
    Hypertension
         subjects affected / exposed
    38 / 292 (13.01%)
    43 / 297 (14.48%)
         occurrences all number
    43
    46
    Hypotension
         subjects affected / exposed
    20 / 292 (6.85%)
    13 / 297 (4.38%)
         occurrences all number
    21
    14
    Nervous system disorders
    Tremor
         subjects affected / exposed
    53 / 292 (18.15%)
    52 / 297 (17.51%)
         occurrences all number
    56
    52
    Headache
         subjects affected / exposed
    23 / 292 (7.88%)
    21 / 297 (7.07%)
         occurrences all number
    27
    27
    Dizziness
         subjects affected / exposed
    15 / 292 (5.14%)
    11 / 297 (3.70%)
         occurrences all number
    17
    14
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    24 / 292 (8.22%)
    34 / 297 (11.45%)
         occurrences all number
    25
    36
    Leukopenia
         subjects affected / exposed
    35 / 292 (11.99%)
    105 / 297 (35.35%)
         occurrences all number
    46
    125
    Neutropenia
         subjects affected / exposed
    7 / 292 (2.40%)
    50 / 297 (16.84%)
         occurrences all number
    9
    60
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    22 / 292 (7.53%)
    24 / 297 (8.08%)
         occurrences all number
    24
    29
    Oedema peripheral
         subjects affected / exposed
    44 / 292 (15.07%)
    47 / 297 (15.82%)
         occurrences all number
    52
    61
    Fatigue
         subjects affected / exposed
    21 / 292 (7.19%)
    34 / 297 (11.45%)
         occurrences all number
    21
    38
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    23 / 292 (7.88%)
    26 / 297 (8.75%)
         occurrences all number
    31
    32
    Nausea
         subjects affected / exposed
    35 / 292 (11.99%)
    37 / 297 (12.46%)
         occurrences all number
    40
    48
    Dyspepsia
         subjects affected / exposed
    19 / 292 (6.51%)
    15 / 297 (5.05%)
         occurrences all number
    20
    17
    Diarrhoea
         subjects affected / exposed
    99 / 292 (33.90%)
    85 / 297 (28.62%)
         occurrences all number
    130
    101
    Constipation
         subjects affected / exposed
    27 / 292 (9.25%)
    31 / 297 (10.44%)
         occurrences all number
    28
    36
    Abdominal pain
         subjects affected / exposed
    21 / 292 (7.19%)
    17 / 297 (5.72%)
         occurrences all number
    22
    17
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    5 / 292 (1.71%)
    22 / 297 (7.41%)
         occurrences all number
    5
    23
    Cough
         subjects affected / exposed
    15 / 292 (5.14%)
    23 / 297 (7.74%)
         occurrences all number
    16
    26
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    16 / 292 (5.48%)
    14 / 297 (4.71%)
         occurrences all number
    17
    14
    Acute kidney injury
         subjects affected / exposed
    15 / 292 (5.14%)
    9 / 297 (3.03%)
         occurrences all number
    16
    10
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    9 / 292 (3.08%)
    17 / 297 (5.72%)
         occurrences all number
    9
    19
    Back pain
         subjects affected / exposed
    18 / 292 (6.16%)
    17 / 297 (5.72%)
         occurrences all number
    19
    18
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    41 / 292 (14.04%)
    45 / 297 (15.15%)
         occurrences all number
    51
    60
    Polyomavirus viraemia
         subjects affected / exposed
    11 / 292 (3.77%)
    16 / 297 (5.39%)
         occurrences all number
    11
    18
    Cytomegalovirus infection
         subjects affected / exposed
    8 / 292 (2.74%)
    15 / 297 (5.05%)
         occurrences all number
    9
    15
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    10 / 292 (3.42%)
    21 / 297 (7.07%)
         occurrences all number
    12
    22
    Metabolic acidosis
         subjects affected / exposed
    16 / 292 (5.48%)
    14 / 297 (4.71%)
         occurrences all number
    17
    15
    Hypophosphataemia
         subjects affected / exposed
    35 / 292 (11.99%)
    36 / 297 (12.12%)
         occurrences all number
    38
    41
    Hypomagnesaemia
         subjects affected / exposed
    41 / 292 (14.04%)
    40 / 297 (13.47%)
         occurrences all number
    44
    47
    Hypokalaemia
         subjects affected / exposed
    19 / 292 (6.51%)
    10 / 297 (3.37%)
         occurrences all number
    22
    10
    Hyperkalaemia
         subjects affected / exposed
    32 / 292 (10.96%)
    38 / 297 (12.79%)
         occurrences all number
    36
    44

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Feb 2018
    Added the LET 240 mg dose group when administered intravenously (IV) without cyclosporin A
    20 Mar 2018
    Added two laboratory exclusion criteria for consistency with the VGCV product circular information
    10 Jul 2018
    Permitted potential participants to be consented and screened up to 5 days (inclusive) after transplant surgery instead of requiring the completion of all screening procedures prior to transplant
    13 Mar 2019
    Added strong and moderate inducers of transporters and/or enzymes to the list of prohibited medications
    23 Oct 2019
    Added the specific requirements for the IV infusion of LET

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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