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    Clinical Trial Results:
    MACH 2 - Magnesium orotate in severe congestive heart failure - Part 2

    Summary
    EudraCT number
    		 2016-004600-53
    Trial protocol
    		 DE  
    Global end of trial date
    04 Sep 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    27 Jun 2025
    First version publication date
    27 Jun 2025
    Other versions
    Summary report(s)
    		 Clinical Trial Report Synopsis

    Trial information

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    Trial identification
    Sponsor protocol code
    RBK03-16-00389
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    WÖRWAG Pharma GmbH & Co. KG
    Sponsor organisation address
    Flugfeld-Allee 24, Böblingen, Germany, 71034
    Public contact
    Global Clinical Research, WÖRWAG Pharma GmbH & Co. KG, 0049 73162040, GCR@woerwagpharma.com
    Scientific contact
    Global Clinical Research, WÖRWAG Pharma GmbH & Co. KG, 0049 7316204416, GCR@woerwagpharma.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
    04 Jun 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Sep 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Sep 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The aim of the study was to demonstrate the significant reduction in NTproBNP by the regular intake of magnesium orotate compared to placebo in participants with HFrEF.
    Protection of trial subjects
    The trial was in compliance with the ethical principles outlined in the Declaration of Helsinki and the International Council for Harmonisation's Good Clinical Practice (ICH GCP) guidelines. Additionally, all local regulatory requirements related to participant safety were followed throughout the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Jun 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 30
    Worldwide total number of subjects
    30
    EEA total number of subjects
    30
    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)
    13
    From 65 to 84 years
    16
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 FPFV 21. November 2019; LPLV 04. September 2023; Recruitment stop due to COVID19 pandemic 06.04.2020 – 22.06.2020; 67 participants were screened and 30 were randomized.

    Pre-assignment
    Screening details
    		 The screening period began once patients had signed the study informed consent. Screening evaluations were performed at baseline visit (V1). After screening, the treatment period started on Visit 1 Day 1.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Data analyst, Carer, Subject, Assessor
    Blinding implementation details
    This was a double-blind, randomized, placebo-controlled cross-over trial. Participants, the investigator, including the whole trial team at trial site and the sponsor, including monitoring and data management personnel were blinded to the identity of the treatment from the time of randomization until official unblinding. Serum magnesium levels were not accessible until database closure.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo - Verum
    Arm description
    		 Day 1-84 Placebo; Day 85-140 Wash-out; Day 141-224 Verum
    Arm type
    		 Crossover: Placebo - Verum

    Investigational medicinal product name
    Magnesium orotate dihydrate
    Investigational medicinal product code
    Other name
    magnerot® CLASSIC N
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was administered orally three times a day as 3 tablets per dose for 4 weeks, followed by 2 tablets per dose for an additional 8 weeks. This was followed by a wash-out phase. Magnesium orotate dihydrate was administered orally three times a day as 3 tablets per dose (4500 mg/day) for 4 weeks, followed by as 2 tablets per dose (3000 mg/day) for an additional 8 weeks.

    Arm title
    		 Verum - Placebo
    Arm description
    		 Day 1-84 Verum; Day 85-140 Wash-out; Day 141-224 Placebo
    Arm type
    		 Crossover: Verum - Placebo

    Investigational medicinal product name
    Magnesium orotate dihydrate
    Investigational medicinal product code
    Other name
    magnerot® CLASSIC N
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Magnesium orotate dihydrate was administered orally three times a day as 3 tablets per dose (4500 mg/day) for 4 weeks, followed by as 2 tablets per dose (3000 mg/day) for an additional 8 weeks.This was followed by a wash-out phase. Placebo was administered orally three times a day as 3 tablets per dose for 4 weeks, followed by 2 tablets per dose for an additional 8 weeks.

    Number of subjects in period 1
    		Placebo - Verum Verum - Placebo
    Started
    15
    15
    Wash-out
    14
    14
    Completed
    13
    14
    Not completed
    2
    1
         Worsening of general condition
    1
    -
         Consent withdrawn by subject
    -
    1
         Protocol deviation
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo - Verum
    Reporting group description
    		 Day 1-84 Placebo; Day 85-140 Wash-out; Day 141-224 Verum

    Reporting group title
    Verum - Placebo
    Reporting group description
    		 Day 1-84 Verum; Day 85-140 Wash-out; Day 141-224 Placebo

    Reporting group values
    		 Placebo - Verum Verum - Placebo Total
    Number of subjects
    		 15 15 30
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 5 8 13
        From 65-84 years
    		 10 6 16
        85 years and over
    		 0 1 1
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 73 (59 to 79) 61 (55 to 71) -
    Gender categorical
    Units: Subjects
        Female
    		 5 5 10
        Male
    		 10 10 20
    Subject analysis sets

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The analysis was carried out "per protocol" (PP), i.e., only those test individuals for whom there are no major protocol violations, who have received a predetermined minimum proportion of the planned treatment (at least 80%) and for whom the examinations required to assess the target criteria have been carried out at predetermined points in time are analysed. In this trial, the per protocol analysis was defined as the primary analysis. Criteria for per protocol analysis were fulfilled by 27 participants. The 3 drop-outs didn’t fulfil the PP criteria and therefore, were not included into efficacy analysis. Day 1-84 Placebo or Verum; Day 85-140 Wash-out; Day 141-224 Verum or Placebo

    Subject analysis set title
    Verum
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The analysis was carried out "per protocol" (PP), i.e., only those test individuals for whom there are no major protocol violations, who have received a predetermined minimum proportion of the planned treatment (at least 80%) and for whom the examinations required to assess the target criteria have been carried out at predetermined points in time are analysed. In this trial, the per protocol analysis was defined as the primary analysis. Criteria for per protocol analysis were fulfilled by 27 participants. The 3 drop-outs didn’t fulfil the PP criteria and therefore, were not included into efficacy analysis. Day 1-84 Placebo or Verum; Day 85-140 Wash-out; Day 141-224 Verum or Placebo

    Subject analysis sets values
    		 Placebo Verum
    Number of subjects
    27
    27
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    12
    12
        From 65-84 years
    14
    14
        85 years and over
    1
    1
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    65.67 (56.00 to 77.00)
    65.67 (56.00 to 77.00)
    Gender categorical
    Units: Subjects
        Female
    9
    9
        Male
    18
    18

    End points

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    End points reporting groups
    Reporting group title
    Placebo - Verum
    Reporting group description
    		 Day 1-84 Placebo; Day 85-140 Wash-out; Day 141-224 Verum

    Reporting group title
    Verum - Placebo
    Reporting group description
    		 Day 1-84 Verum; Day 85-140 Wash-out; Day 141-224 Placebo

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The analysis was carried out "per protocol" (PP), i.e., only those test individuals for whom there are no major protocol violations, who have received a predetermined minimum proportion of the planned treatment (at least 80%) and for whom the examinations required to assess the target criteria have been carried out at predetermined points in time are analysed. In this trial, the per protocol analysis was defined as the primary analysis. Criteria for per protocol analysis were fulfilled by 27 participants. The 3 drop-outs didn’t fulfil the PP criteria and therefore, were not included into efficacy analysis. Day 1-84 Placebo or Verum; Day 85-140 Wash-out; Day 141-224 Verum or Placebo

    Subject analysis set title
    Verum
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The analysis was carried out "per protocol" (PP), i.e., only those test individuals for whom there are no major protocol violations, who have received a predetermined minimum proportion of the planned treatment (at least 80%) and for whom the examinations required to assess the target criteria have been carried out at predetermined points in time are analysed. In this trial, the per protocol analysis was defined as the primary analysis. Criteria for per protocol analysis were fulfilled by 27 participants. The 3 drop-outs didn’t fulfil the PP criteria and therefore, were not included into efficacy analysis. Day 1-84 Placebo or Verum; Day 85-140 Wash-out; Day 141-224 Verum or Placebo

    Primary: Change of NTproBNP

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    End point title
    		 Change of NTproBNP
    End point description
    Differences on the change of NTproBNP between Verum and Placebo after 12 weeks of treatment.
    End point type
    Primary
    End point timeframe
    Visit 1 to visit 3 (12 weeks)
    End point values
    		 Placebo Verum
    Number of subjects analysed
    27
    27
    Units: pg/ml
        median (inter-quartile range (Q1-Q3))
    -199.0 (-368.0 to 18.0)
    -70.0 (-291.0 to 174.0)
    Statistical analysis title
    		 Change of NTproBNP: Verum vs. Placebo
    Comparison groups
    Verum v Placebo
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 = 0.486
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [1] - As it is a cross-over study, in total 27 participants were analysed and every one received Placebo and Verum for 12 weeks.

    Secondary: Change of LVEF

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    End point title
    		 Change of LVEF
    End point description
    Difference on change of Left Ventricular Ejection Fraction (LVEF) under Verum and Placebo after 12 weeks of treatment.
    End point type
    Secondary
    End point timeframe
    Visit 1 to visit 3 (12 weeks)
    End point values
    		 Placebo Verum
    Number of subjects analysed
    27
    27
    Units: %
        median (inter-quartile range (Q1-Q3))
    0 (-2.0 to 4.0)
    1 (-3.0 to 4.0)
    Statistical analysis title
    		 Change of LVEF: Verum vs. Placebo
    Comparison groups
    Placebo v Verum
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    P-value
    		 = 0.776
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [2] - As this is a cross-over study, 27 participants were analyzed, with each participant receiving Verum or Placebo for 12 weeks.

    Secondary: Change of KCCQ questionnaire OSS

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    End point title
    		 Change of KCCQ questionnaire OSS
    End point description
    Differences on the change KCCQ questionnaire Overall Summary Score (OSS) under Verum and Placebo after 12 weeks of treatment.
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 3 (12 weeks)
    End point values
    		 Placebo Verum
    Number of subjects analysed
    27
    27
    Units: Change of score
        median (inter-quartile range (Q1-Q3))
    0 (-5.729 to 4.688)
    1.771 (-2.344 to 5.208)
    Statistical analysis title
    		 Change of KCCQ OSS: Verum vs. Placebo
    Comparison groups
    Placebo v Verum
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    P-value
    		 = 0.564
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [3] - As this is a cross-over study, 27 participants were analyzed, with each participant receiving Verum or Placebo for 12 weeks.

    Secondary: Change of KCCQ questionnaire CSS

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    End point title
    		 Change of KCCQ questionnaire CSS
    End point description
    Differences on the change KCCQ questionnaire Clinical Summary Score (CSS) under Verum and Placebo after 12 weeks of treatment.
    End point type
    Secondary
    End point timeframe
    Visit 1 to visit 3 (12 weeks)
    End point values
    		 Placebo Verum
    Number of subjects analysed
    27
    27
    Units: Change of score
        median (inter-quartile range (Q1-Q3))
    -1.04 (-5.21 to 4.17)
    0 (-6.25 to 8.85)
    Statistical analysis title
    		 Change of KCCQ CSS: Verum vs. Placebo
    Comparison groups
    Verum v Placebo
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    P-value
    		 = 0.435
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [4] - As this is a cross-over study, 27 participants were analyzed, with each participant receiving Verum or Placebo for 12 weeks.

    Secondary: Change of EQ-5D-5L VAS

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    End point title
    		 Change of EQ-5D-5L VAS
    End point description
    Differences on the change EQ-5D-5L (Visual Analog Scale) VAS under Verum and Placebo after 12 weeks of treatment.
    End point type
    Secondary
    End point timeframe
    Visit 1 to visit 3 (12 weeks)
    End point values
    		 Placebo Verum
    Number of subjects analysed
    27
    27
    Units: Score change
        median (inter-quartile range (Q1-Q3))
    0.000 (-5.000 to 5.000)
    1.000 (0.000 to 10.000)
    Statistical analysis title
    		 Change of EQ-5D-5L VAS: Verum vs. Placebo
    Comparison groups
    Placebo v Verum
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    P-value
    		 = 0.152
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [5] - As this is a cross-over study, 27 participants were analyzed, with each participant receiving Verum or Placebo for 12 weeks.

    Secondary: Change of EQ-5D-5L Index

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    End point title
    		 Change of EQ-5D-5L Index
    End point description
    Differences on the change EQ-5D-5L Index under Verum and Placebo after 12 weeks of treatment.
    End point type
    Secondary
    End point timeframe
    Visit 1 to visit 3 (12 weeks)
    End point values
    		 Placebo Verum
    Number of subjects analysed
    27
    27
    Units: Score change
        median (inter-quartile range (Q1-Q3))
    0.000 (-0.049 to 0.057)
    0.000 (0.000 to 0.050)
    Statistical analysis title
    		 Change of EQ-5D-5L Index: Verum vs. Placebo
    Comparison groups
    Placebo v Verum
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 other [6]
    P-value
    		 = 0.274
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [6] - As this is a cross-over study, 27 participants were analyzed, with each participant receiving Verum or Placebo for 12 weeks.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Timeframe for reporting adverse events: Adverse events were collected from first dose of study treatment until end of study at week 32.
    Adverse event reporting additional description
    Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment. Adverse events are evaluated in the safety analysis set that includes all participants who received at least one dose of the investigational medicinal product.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Verum
    Reporting group description
    		 Reported adverse events occurred during intake of magnesium orotate dihydrate.

    Reporting group title
    Placebo
    Reporting group description
    		 Reported adverse events occurred during intake of Placebo.

    Reporting group title
    Wash-out after Verum
    Reporting group description
    		 Reported adverse events occurred during wash-out after magnesium orotate dihydrate.

    Reporting group title
    Wash-out after Placebo
    Reporting group description
    		 Reported adverse events occurred during wash-out after Placebo.

    Reporting group title
    N/A, occured after trial discontinuation
    Reporting group description
    		 Reported adverse events occurred after end of trial. For one participant who dropped out of the trial 12 events including 9 SAEs were documented after end of trial, as part of an SAE follow-up. For another dropout participant one AE was documented after end of treatment with start date on the same day as the last visit.

    Serious adverse events
    		 Verum Placebo Wash-out after Verum Wash-out after Placebo N/A, occured after trial discontinuation
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 30 (16.67%)
    1 / 30 (3.33%)
    2 / 30 (6.67%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Failed weaning from the ventilator
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative renal failure
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Distal radius fracture
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Acute occlusion of left arteria poplitea
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiovascular collapse
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Independent shock delivery by ICD (implanted cardioverter defibrillator)
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiorenal syndrome
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Normofrequent atrial flutter
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NSTEMI
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericard effusion
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Possible critical illness neuropathy
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Appendicitis epiploica
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epigastric pain
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacterial infection
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fungal infection
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterobacter cloacae infection
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Verum Placebo Wash-out after Verum Wash-out after Placebo N/A, occured after trial discontinuation
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 30 (90.00%)
    24 / 30 (80.00%)
    12 / 30 (40.00%)
    12 / 30 (40.00%)
    2 / 30 (6.67%)
    Vascular disorders
    Vascular disorders
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    1
    0
    1
    Surgical and medical procedures
    Surgical and medical procedures
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    General disorders and administration site conditions
    General disorders and administration site conditions
         subjects affected / exposed
    5 / 30 (16.67%)
    6 / 30 (20.00%)
    0 / 30 (0.00%)
    2 / 30 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    6
    10
    0
    2
    0
    Respiratory, thoracic and mediastinal disorders
    Respiratory, thoracic, and mediastinal disorders
         subjects affected / exposed
    4 / 30 (13.33%)
    6 / 30 (20.00%)
    4 / 30 (13.33%)
    2 / 30 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    6
    9
    4
    3
    0
    Psychiatric disorders
    Psychiatric disorders
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    0
    0
    1
    Investigations
    Examinations
         subjects affected / exposed
    9 / 30 (30.00%)
    5 / 30 (16.67%)
    6 / 30 (20.00%)
    5 / 30 (16.67%)
    0 / 30 (0.00%)
         occurrences all number
    11
    9
    17
    6
    0
    Injury, poisoning and procedural complications
    Injury, poisoning, and procedure-related complications
         subjects affected / exposed
    1 / 30 (3.33%)
    4 / 30 (13.33%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    4
    4
    1
    1
    0
    Cardiac disorders
    Cardiac disorders
         subjects affected / exposed
    8 / 30 (26.67%)
    10 / 30 (33.33%)
    10 / 30 (33.33%)
    6 / 30 (20.00%)
    0 / 30 (0.00%)
         occurrences all number
    21
    17
    18
    7
    0
    Nervous system disorders
    Nervous system disorders
         subjects affected / exposed
    7 / 30 (23.33%)
    5 / 30 (16.67%)
    3 / 30 (10.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    9
    7
    3
    1
    0
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    1
    1
    0
    Eye disorders
    Eye disorders
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    Gastrointestinal disorders
         subjects affected / exposed
    12 / 30 (40.00%)
    9 / 30 (30.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    24
    13
    0
    2
    1
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders
         subjects affected / exposed
    1 / 30 (3.33%)
    4 / 30 (13.33%)
    2 / 30 (6.67%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    5
    2
    0
    0
    Renal and urinary disorders
    Renal and urinary disorders
         subjects affected / exposed
    2 / 30 (6.67%)
    4 / 30 (13.33%)
    2 / 30 (6.67%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    4
    3
    1
    0
    Endocrine disorders
    Endocrine disorders
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    1
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Musculoskeletal, connective tissue, and bone disorders
         subjects affected / exposed
    4 / 30 (13.33%)
    11 / 30 (36.67%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    4
    18
    1
    0
    0
    Infections and infestations
    Infections and infestations
         subjects affected / exposed
    2 / 30 (6.67%)
    4 / 30 (13.33%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    4
    1
    1
    0
    Metabolism and nutrition disorders
    Metabolism and nutrition disorders
         subjects affected / exposed
    5 / 30 (16.67%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    5
    1
    1
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 May 2018
    Implementation of changes required for regulatory approval
    10 Jul 2018
    Principal investigator change
    31 Jan 2019
    In- and exclusion criteria change
    22 Mar 2019
    Implementation of changes required for regulatory approval
    07 Jun 2019
    In- and exclusion criteria change
    01 Oct 2020
    Extension of trial duration, adjustment of statistics details.
    20 Jun 2022
    Principal investigator and deputy change, extension of trial duration

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    06 Apr 2020
    Recruitment stop due to COVID19 pandemic 06.04.2020 – 22.06.2020
    22 Jun 2020

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Small number of participants (pilot study)
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    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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