Clinical Trial Results:
Pilot single‐arm clinical trial to evaluate the efficacy, PK interactions and safety of dolutegravir plus 2 NRTIs in HIV‐1‐infected solid organ transplant patients
Summary
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EudraCT number |
2017-000469-62 |
Trial protocol |
ES |
Global end of trial date |
21 May 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Aug 2025
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First version publication date |
21 Aug 2025
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
DTG-SOT
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03360682 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Fundació Clínic per a la Recerca Biomèdica
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Sponsor organisation address |
C/ Rosselló, 149-153, Barcelona, Spain, 08036
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Public contact |
CTU, CTU Clinic (Clinical Trial Unit), +34 9322754009838, acruceta@recerca.clinic.cat
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Scientific contact |
CTU, CTU Clinic (Clinical Trial Unit), +34 9322754009838, acruceta@recerca.clinic.cat
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
21 May 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 May 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
21 May 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The aims of this study are to obtain pharmacokinetic data on interactions between DTG and immunosuppressant drugs (Cyclosporine A, Tacrolimus, Syrolimus and Mycophenolic acid) in SOT recipients To provide proof of principle data that DTG plus 2 NUCs is safe and effective in HIV‐infected SOT recipients.
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Protection of trial subjects |
The study was conducted in accordance with the Royal Decree 1090/2015 (Spain), ICH-GCP (International Conference on Harmonisation – Good Clinical Practice) and The Declaration of Helsinki (latest version, Fortaleza 2013). Before initiation, the following approvals were required: Ethics Committee approval, Authorization from the Spanish Medicines Agency (AEMPS), Institutional approval and
Acceptance by the sponsor and coordinating investigator.
All participants had to provide signed and dated informed consent before any study procedures; Received written and verbal information about the study’s nature, duration, purpose, and potential risks;
Have the right to withdraw at any time without penalty; Had guaranteed continuous medical and nursing supervision throughout the study. The protocol also follows UNAIDS Good Participatory Practice Guidelines, involving community representatives in the design of the protocol and patient information materials.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Apr 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 19
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Worldwide total number of subjects |
19
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EEA total number of subjects |
19
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
19
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
Pre-assignment
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Screening details |
HIV-1-infected adults (>18) with kidney, liver, or heart transplant, on stable ART ≥6 months, HIV RNA <50 c/mL for 12 months, no major resistance mutations, and HLA-B*5701 negative. Excluded: ART failure, contraindicated meds, active infections, cancer, pregnancy, or drug intolerance. | ||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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DTG + 2 NRTIs | ||||||||||
Arm description |
Dolutegravir plus 2 NRTIs in HIV-1-infected solid organ transplant recipients | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Dolutegravir/ Abacavir/ Lamivudina (DTG/ABC/3TC)
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Investigational medicinal product code |
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Other name |
Triumeq®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dolutegravir 50mg + Abacavir 600 mg + Lamivudina 300 mg + (1 tablet once daily)
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Investigational medicinal product name |
Dolutegravir (DTG) + Emtricitabina/ Tenofovir (FTC/TDF)
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Investigational medicinal product code |
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Other name |
Truvada® + Tivicay®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Emtricitabina 200 mg/ Tenofovir 245 mg (Truvada®, 1 tablet once daily)
Dolutegravir 50 mg (Tivicay®, 1 tablet once daily)
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
DTG + 2 NRTIs
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Reporting group description |
Dolutegravir plus 2 NRTIs in HIV-1-infected solid organ transplant recipients | ||
Subject analysis set title |
Pharmacokinetic (PK) subset before ART change
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants who underwent pharmacokinetic sampling before switching to DTG-based ART (n = 9).
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Subject analysis set title |
Pharmacokinetic (PK) subset after 2wk ART change
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants who underwent pharmacokinetic sampling after 2 weeks switching to DTG-based ART (n = 9).
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End point title |
Change in pharmacokinetic parameters (Cmax, Cmin, T, AUC) of CsA immunosuppressant [1] | ||||||||||||||||||||||||
End point description |
Change in pharmacokinetic parameters (Cmax, Cmin, T, AUC) of immunosuppressant Cyclosporine A (CsA)
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End point type |
Primary
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End point timeframe |
2 weeks after switching from raltegravir-based ART to dolutegravir-based ART
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The change in CsA pharmacokinetic parameters was analyzed using the Wilcoxon signed-rank test for paired samples. This non-parametric test was selected due to the small sample size (n = 2) and non-normal distribution of the data. Results were reported as median and interquartile range (IQR), and a two-tailed p-value < 0.05 was considered statistically significant. |
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No statistical analyses for this end point |
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End point title |
Change in pharmacokinetic parameters (Cmax, Cmin, T, AUC) of MPA immunosuppressant [2] | ||||||||||||||||||||||||
End point description |
Change in pharmacokinetic parameters (Cmax, Cmin, T, AUC) of immunosuppressant Mycophenolic Acid (MPA).
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End point type |
Primary
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End point timeframe |
2 weeks after switching from raltegravir-based ART to dolutegravir-based ART
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The change in MPA pharmacokinetic parameters was analyzed using the Wilcoxon signed-rank test for paired samples. This non-parametric test was selected due to the small sample size (n = 7) and non-normal distribution of the data. Results were reported as median and interquartile range (IQR), and a two-tailed p-value < 0.05 was considered statistically significant. |
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No statistical analyses for this end point |
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End point title |
Change in pharmacokinetic parameters (Cmax, Cmin, T, AUC) of Tacrolimus immunosuppressant [3] | ||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
2 weeks after switching from raltegravir-based ART to dolutegravir-based ART
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The change in Tacrolimus pharmacokinetic parameters was analyzed using the Wilcoxon signed-rank test for paired samples. This non-parametric test was selected due to the small sample size (n = 2) and non-normal distribution of the data. Results were reported as median and interquartile range (IQR), and a two-tailed p-value < 0.05 was considered statistically significant. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
All AEs will be recorded by the Investigator from the time the subject signs informed consent until the last study visit or to 28 days after the last dose of IMP in case of early withdrawal while patient is receiving IMP.
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Adverse event reporting additional description |
Only adverse events leading to treatment discontinuation or considered clinically relevant are reported individually. All other AEs occurred with low frequency and were not considered related to treatment.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
28.0
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Reporting groups
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Reporting group title |
DTG plus 2NRTIs
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
DTG plus 2 NRTIs: lack clinically significant drug–drug interactions with calcineurin inhibitors (tacrolimus) and MPA in PHIV SOT recipients. Sample size for the PK analysis of CsA (n = 2): insufficient to draw robust conclusions. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/40256046 |