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| ID | Type | Description | Link |
|---|---|---|---|
| 20730 | Registry Identifier | DAIDS-ES Registry Number |
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Maraviroc (MVC) is a type of HIV medicine called a CCR5 inhibitor. This study will evaluate the safety and tolerability of MVC in HIV-infected adults receiving a kidney transplant.
MVC is a CCR5 inhibitor that may have a positive role in modulating the immune response following transplantation. The purpose of this study is to evaluate the safety and tolerability of MVC in HIV-infected adults in need of a kidney transplant. The study will also evaluate whether using both immunosuppressant drugs and MVC will improve kidney function after a kidney transplant.
This study will enroll HIV-infected adults on combination antiretroviral therapy (cART) who need a kidney transplant. At the time of their kidney transplant, study participants will be randomly assigned to receive either MVC or placebo as an addition to their cART regimen. (MVC or placebo will be provided by the study. However, the HIV medicines in their cART regimens will not be provided by the study.) Participants will receive MVC or placebo throughout their participation in the study, which will be 1 to 3 years depending on when they enroll in the study.
Study visits will occur at enrollment (Day 0) and post-transplant Weeks 1, 2, 4, 8, 13, 26, 39, 52, 78, 104, 130, and 156. Study visits may include a physical examination, blood collection, lymph node collection, urine sample collection, and a kidney biopsy. During the study, participants will also be monitored closely for evidence of drug toxicities, HIV treatment failure and rejection.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Maraviroc (MVC) | Experimental | Participants will receive MVC at the time of admission for transplantation and prior to transplant. Participants will receive MVC throughout their participation in the study, which will be 1 to 3 years depending on when they enroll. |
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| Arm 2: Placebo | Placebo Comparator | Participants will receive placebo at the time of admission for transplantation and prior to transplant. Participants will receive placebo throughout their participation in the study, which will be 1 to 3 years depending on when they enroll. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Maraviroc | Drug | Initial dose of 300 mg twice daily (150mg twice daily if co-prescribed with a potent CYP3A inhibitor or 600mg twice daily if co-prescribed with a potent CYP3A inducer). Will be modified if GFR < 30, if co-prescribed with a potent CYP3A inhibitor or inducer, or if the calcineurin inhibitor used for maintenance immunosuppression is changed to cyclosporine (which is only allowed for tacrolimus toxicity). Once GFR is greater than or equal to 30, the dose should be returned to the non-renal dosage. If GFR is consistently fluctuating (especially immediately post-transplant), the site investigator may choose when to resume normal dosing of study product based on clinical assessment of stability. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Glomerular Filtration Rate by Iohexol Clearance at Week 52 | The primary efficacy endpoint is the 52-week GFR as measured by iohexol clearance | Measured at Week 52 Post-transplant |
| Cumulative Incidence of Graft Loss, Toxicities ≥ Grade 3 Per the DAIDS Toxicity Table and/or Permanent Treatment Discontinuation | The primary safety endpoint will be the incidence of graft loss and toxicities ≥ Grade 3 and/or permanent treatment discontinuation within the first 52 weeks post-transplant | Measured through Week 52 Post-transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Mean CD45 Gene Expression Count (PTPRC) | Based on the formalin-fixed paraffin-embedded (FFPE) kidney biopsy sample. CD45 RNA In Situ Hybridization was performed, and the CD45 gene expression count is calculated by counting the "spots" (the RNA signal) in QuPath and then dividing the number of spots by biopsy tissue area in mm². | Measured at Week 26 Post-transplant |
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Inclusion Criteria:
Participant is able to understand and provide informed consent.
Documented HIV infection (by any licensed enzyme-linked immunosorbent assay [ELISA] and confirmation by Western Blot, positive HIV antibody (ab) indirect fluorescent antibody (IFA), or documented history of detectable HIV-1 RNA).
Participant is 18 years of age or older.
CD4+ T-cell count greater than or equal to 200/µL at any time in the 26 weeks prior to enrollment.
Most recent HIV-1 RNA less than 50 copies RNA/mL. Eligibility at the time of enrollment will be determined based on the most recent HIV-1 RNA, not more than 26 weeks prior to enrollment. Subjects who require a switch in combination antiretroviral therapy (cART) regimen to become study eligible must also have an eligible HIV-1 RNA result post change in cART.
Participant meets standard listing criteria for placement on transplant waiting list.
For participants with an HIV+ deceased donor:
Antiretroviral (ARV) Use: Participant is on a stable cART regimen for at least 3 months prior to enrollment (unless changes are made due to toxicity, drug interactions, convenience or to an eligible non-protease inhibitor-based regimen). Switch should not be due to virologic failure. A regimen consisting of 2 NTRTIs and an integrase inhibitor is preferred due to minimal drug interaction but any non-protease inhibitor regimen may be used.
No known allergy or intolerance to components of maraviroc (MVC) or its formulation.
No known contraindication to MVC.
Female participants of child-bearing potential must have a negative serum beta-human chorionic gonadotropin (HCG) pregnancy test within 30 days of randomization.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peter Stock, MD, PhD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UAB HIVTR-CCR5 Non-Network CRS | Birmingham | Alabama | 35233-2060 | United States | ||
| UCLA HIVTR-CCR5 Non-Network CRS |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: Maraviroc (MVC) | Participants who were assigned to and received Maraviroc in the study. |
| FG001 | Arm 2: Placebo | Participants who were assigned to and received Placebo in the study. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 28, 2019 |
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| Placebo | Drug | Initial dose of 300 mg twice daily (150mg twice daily if co-prescribed with a potent CYP3A inhibitor or 600mg twice daily if co-prescribed with a potent CYP3A inducer). Will be modified if GFR < 30, if co-prescribed with a potent CYP3A inhibitor or inducer, or if the calcineurin inhibitor used for maintenance immunosuppression is changed to cyclosporine (which is only allowed for tacrolimus toxicity). Once GFR is greater than or equal to 30, the dose should be returned to the non-renal dosage. If GFR is consistently fluctuating (especially immediately post-transplant), the site investigator may choose when to resume normal dosing of study product based on clinical assessment of stability. |
|
| Mean CD45 Quantitative Immunohistochemistry (IHC) | Mean CD45 quantitative immunohistochemistry (IHC) based on FFPE sample | Measured at Week 26 Post-transplant |
| Tissue Common Rejection Module (tCRM) Score Using the 11-gene tCRM Module on FFPE Biopsy Shaves | Tissue Common Rejection Module (tCRM) score using the 11-gene tCRM module on FFPE biopsy shaves at 26 weeks. The score measures the average (geometric mean) gene expression level of CRM genes (BASP1, CD6, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, TAP1) in kidney tissue. Possible range (min-max) for the tCRM score is 0.01 - 15.0, with higher values representing worse outcomes. | Measured at Week 26 Post-transplant |
| Urine Common Rejection Module (uCRM) Score Using the 11-gene uCRM Module on Urine Cell Pellets | Urine Common Rejection Module (uCRM) score using the 11-gene uCRM module on urine cell pellets at week 26. The score measures the average (geometric mean) gene expression level of CRM genes (BASP1, CD6, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, TAP1) in urine sediment. Possible range (min-max) for the uCRM score is 0.01 - 15.0, with higher values representing worse outcomes. | Measured at Week 26 Post-transplant |
| Urine Common Rejection Module (uCRM) Score Using the 11-gene uCRM Module on Urine Cell Pellets | Urine Common Rejection Module (uCRM) score using the 11-gene uCRM module on urine cell pellets at week 52. The score measures the average (geometric mean) gene expression level of CRM genes (BASP1, CD6, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, TAP1) in urine sediment. Possible range (min-max) for the uCRM score is 0.01 - 15.0, with higher values representing worse outcomes. | Measured at Week 52 Post-transplant |
| Proportion of Participants With Estimated Glomerular Filtration Rate (eGFR) Less Than 60 mL/Min/1.73 m² at Week 52 | Measured by Chronic Kidney Disease Epidemiology collaboration equation (CKD-EPI) Creatinine equation | Measured at Week 52 Post-transplant |
| Proportion of Participants With Defined CKD Stage 4 or 5 at Year 1 | Proportion of participants with defined CKD stage 4 or 5 at week 52 post-transplant. CKD Stage 4 or 5 is defined as a glomerular filtration rate (GFR) of <30 mL/min. | Year 1 time point |
| Mean eGFR at Week 52 Based on CKD-EPI Creatinine Equation | Mean eGFR at Week 52 calculated by CKD-EPI creatinine equation | Measured at Week 52 Post-transplant |
| The Slope of eGFR Over Time in Year 1 | The slope of eGFR over time in Year 1, calculated by CKD-EPI Creatinine equation. Slope is computed via the repeated measures analysis, covering the study time points of weeks 13, 26, 39 and 52. The estimated average slope (and corresponding 95% confidence interval) is provided for incremental progression from one time point to the next (i.e., the displayed slope shows the extent of increase (positive) or decrease (negative) in eGFR level per every time point (13 weeks) elapsed. | Time points in Year 1 (four time points: weeks 13, 26, 39, 52) |
| HIV DNA in Peripheral Blood CD4+ T Cells at Week 52 | HIV DNA in peripheral blood CD4+ T cells at Week 52. The standard ACTG type extraction protocol was used to extract DNA from PBMC. The readout was copies of cellular HIV-1 DNA per million PBMC. Subsequently, the outcome measure/value was obtained by multiplying the readout by the participant's CD4 percentage level at that time point, to obtain the measure of copies of HIV-1 DNA per million peripheral blood CD4+ T cells | At week 52 post-transplant |
| HIV RNA in Peripheral Blood CD4+ T Cells at Week 52. | HIV RNA in peripheral blood CD4+ T cells at Week 52. The standard ACTG type extraction protocol was used to extract RNA from PBMC. The readout was copies of cellular HIV-1 RNA per million PBMC. Subsequently, the outcome measure/value was obtained by multiplying the readout by the participant's CD4 percentage level at that time point, to obtain the measure of copies of HIV-1 RNA per million peripheral blood CD4+ T cells | Week 52 Post Transplant |
| Plasma HIV RNA Levels (Single Copy Assay) at Week 52 | Plasma HIV RNA levels (single copy assay) at Week 52 Post-transplant | Week 52 Post-transplant |
| Cumulative Incidence/Proportion of Biopsy Proven Acute Rejection Within 1 Year Post Transplant | Defined by histologic evidence of rejection and graft dysfunction as identified on central read of biopsy slides as well as on site biopsies. When a central read of biopsy slide is available, those results will be used; in its absence, site biopsy result will be used. Both acute cellular and humoral rejections were considered for this outcome measure, but borderline results were excluded. | Within Year 1 Post-transplant |
| Cumulative Incidence/Proportion of Acute Cellular Rejection Grade Equal to or Greater Than 1A During the Entire Study Follow-up | Measured by the Banff 2007 criteria as identified on central read of biopsy slides; for site biopsy results, grading was not available, all results except for borderline results were assumed to be grade 1A or greater. If available, central read result was used; if not, site biopsy result was used. | Within 3 years post-transplant |
| Incidence/Proportion of Antibody Mediated Rejection | Incidence of humoral/antibody mediated rejection within 52 weeks of the transplant. Both central reads and site biopsy results were included, and central read result was used if one was available, and if not, the site biopsy result was used. | Within 52 weeks post transplant |
| Proportion of Participants With de Novo Anti-donor Human Leukocyte Antigen (HLA) Antibodies | Proportion of participants with de novo anti-donor human leukocyte antigen (HLA) antibodies at Week 52 | Measured at Week 52 |
| Incidence/Proportion of Participants With HIV Infection in the Renal Allograft | Histology/in situ hybridization was used to assess HIV infection in the renal allograft and calculate the proportion of participants with HIV infection | Month 6 Post-transplant |
| Incidence of Death at Year 1 | Incidence of death within Year 1 post-transplant | Within Year 1 Post-transplant |
| Incidence of Graft Loss in Year 1 | Incidence of graft loss within Year 1 post-transplant. | Within Year 1 Post-transplant |
| Incidence of All Adverse Events (AEs) Greater Than or Equal to Grade 3 at Year 1 | Incidence of all adverse events (AEs) greater than or equal to Grade 3 within 1 year post-transplant | Within Year 1 Post-transplant |
| Incidence of Serious Adverse Events (SAEs) Greater Than or Equal to Grade 3 Within Year 1 | Incidence of serious adverse events (SAEs) greater than or equal to Grade 3 within 1 year post-transplant | Within Year 1 Post-transplant |
| Incidence of Opportunistic Infections or Neoplasms Within Year 1 | Incidence of opportunistic infections or neoplasms within 1 year post-transplant | Within Year 1 Post-transplant |
| Incidence of Non-opportunistic Infections Requiring Hospitalization Within Year 1 | Incidence of non-opportunistic infections requiring hospitalization within 1 year post-transplant | Within Year 1 Post-transplant |
| Calcineurin Inhibitor (Tacrolimus) Trough Levels for Participants on Maraviroc Versus Placebo | Calcineurin inhibitor (tacrolimus) trough levels, from 0-12 hours post-dose at month 3 post-transplant for a subset of participants enrolled at UCSF | Month 3 Post-transplant (0-12 hours post-dose) |
| Calcineurin Inhibitor (Tacrolimus) AUC for Participants on Maraviroc Versus Placebo | Calcineurin inhibitor (tacrolimus) AUC, 0-12 hours post-dose at month 3 post-transplant for a subset of participants enrolled at UCSF | Month 3 Post-transplant (0-12 hours post-dose) |
| AUC of CCR5 Blockade (Maraviroc) | AUC of CCR5 blockade (maraviroc), 0-12 hours post-dose at month 3 post-transplant in a subset of participants enrolled at UCSF | Month 3 Post-transplant (0-12 hours post-dose) |
| Trough Levels of CCR5 Blockade (Maraviroc) | Trough levels of CCR5 blockade (maraviroc) from 0-12 hours post-dose testing at month 3 post-transplant in a subset of participants enrolled at UCSF | Month 3 Post-transplant (0-12 hours post-dose) |
| Los Angeles |
| California |
| 90024 |
| United States |
| UCSF HIVTR-CCR5 Non-network CRS | San Francisco | California | 94118 | United States |
| Georgetown HIVTR-CCR5 Non-Network CRS | Washington D.C. | District of Columbia | 20007 | United States |
| Emory HIVTR-CCR5 Non-Network CRS | Atlanta | Georgia | 30322 | United States |
| Northwestern HIVTR-CCR5 Non-Network CRS | Chicago | Illinois | 60611-2927 | United States |
| Univ. of Maryland HIVTR-CCR5 Non-Network CRS | Baltimore | Maryland | 21201 | United States |
| JHU HIVTR-CCR5 Non-Network CRS | Baltimore | Maryland | 21287 | United States |
| Mt. Sinai Med. Ctr. HIVTR-CCR5 Non-Network CRS | New York | New York | 10029 | United States |
| Univ. of Penn HIVTR-CCR5 Non-network CRS | Philadelphia | Pennsylvania | 19104 | United States |
| COMPLETED | Provided at least 1-year survival data, completing the requirement for at least 1-3 years of follow-up in the study |
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| NOT COMPLETED |
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The analysis population includes all subjects who were randomized, received at least 1 dose of Maraviroc or Placebo, and underwent kidney transplant.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1: Maraviroc (MVC) | Participants who were assigned to and received Maraviroc in the study. |
| BG001 | Arm 2: Placebo | Participants who were assigned to and received Placebo in the study. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Glomerular Filtration Rate by Iohexol Clearance at Week 52 | The primary efficacy endpoint is the 52-week GFR as measured by iohexol clearance | Included Full Analysis Population participants with available 52-week GFR level | Posted | Mean | 95% Confidence Interval | mL/min/1.73 m² | Measured at Week 52 Post-transplant |
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| Primary | Cumulative Incidence of Graft Loss, Toxicities ≥ Grade 3 Per the DAIDS Toxicity Table and/or Permanent Treatment Discontinuation | The primary safety endpoint will be the incidence of graft loss and toxicities ≥ Grade 3 and/or permanent treatment discontinuation within the first 52 weeks post-transplant | Posted | Number | 95% Confidence Interval | Proportion (KM estimate for incidence) | Measured through Week 52 Post-transplant |
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| Secondary | Mean CD45 Gene Expression Count (PTPRC) | Based on the formalin-fixed paraffin-embedded (FFPE) kidney biopsy sample. CD45 RNA In Situ Hybridization was performed, and the CD45 gene expression count is calculated by counting the "spots" (the RNA signal) in QuPath and then dividing the number of spots by biopsy tissue area in mm². | Full Analysis Population | Posted | Median | Inter-Quartile Range | spots/mm² | Measured at Week 26 Post-transplant |
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| Secondary | Mean CD45 Quantitative Immunohistochemistry (IHC) | Mean CD45 quantitative immunohistochemistry (IHC) based on FFPE sample | Full Analysis Population | Posted | Median | Inter-Quartile Range | cells/mm² | Measured at Week 26 Post-transplant |
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| Secondary | Tissue Common Rejection Module (tCRM) Score Using the 11-gene tCRM Module on FFPE Biopsy Shaves | Tissue Common Rejection Module (tCRM) score using the 11-gene tCRM module on FFPE biopsy shaves at 26 weeks. The score measures the average (geometric mean) gene expression level of CRM genes (BASP1, CD6, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, TAP1) in kidney tissue. Possible range (min-max) for the tCRM score is 0.01 - 15.0, with higher values representing worse outcomes. | Full Analysis Population - subset of participants with available data at 26 weeks. | Posted | Median | Inter-Quartile Range | score on a scale | Measured at Week 26 Post-transplant |
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| Secondary | Urine Common Rejection Module (uCRM) Score Using the 11-gene uCRM Module on Urine Cell Pellets | Urine Common Rejection Module (uCRM) score using the 11-gene uCRM module on urine cell pellets at week 26. The score measures the average (geometric mean) gene expression level of CRM genes (BASP1, CD6, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, TAP1) in urine sediment. Possible range (min-max) for the uCRM score is 0.01 - 15.0, with higher values representing worse outcomes. | Full Analysis Population - subset of participants with available data at Week 26 | Posted | Median | Inter-Quartile Range | score on a scale | Measured at Week 26 Post-transplant |
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| Secondary | Urine Common Rejection Module (uCRM) Score Using the 11-gene uCRM Module on Urine Cell Pellets | Urine Common Rejection Module (uCRM) score using the 11-gene uCRM module on urine cell pellets at week 52. The score measures the average (geometric mean) gene expression level of CRM genes (BASP1, CD6, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, TAP1) in urine sediment. Possible range (min-max) for the uCRM score is 0.01 - 15.0, with higher values representing worse outcomes. | Full Analysis Population - subset of participants with available data at Week 52 | Posted | Median | Inter-Quartile Range | score on a scale | Measured at Week 52 Post-transplant |
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| Secondary | Proportion of Participants With Estimated Glomerular Filtration Rate (eGFR) Less Than 60 mL/Min/1.73 m² at Week 52 | Measured by Chronic Kidney Disease Epidemiology collaboration equation (CKD-EPI) Creatinine equation | Full Analysis Population participants with available data at Week 52. | Posted | Number | 95% Confidence Interval | Proportion | Measured at Week 52 Post-transplant |
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| Secondary | Proportion of Participants With Defined CKD Stage 4 or 5 at Year 1 | Proportion of participants with defined CKD stage 4 or 5 at week 52 post-transplant. CKD Stage 4 or 5 is defined as a glomerular filtration rate (GFR) of <30 mL/min. | Participants in the Full Analysis population with available data at Year 1 | Posted | Number | 95% Confidence Interval | Proportion of participants | Year 1 time point |
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| Secondary | Mean eGFR at Week 52 Based on CKD-EPI Creatinine Equation | Mean eGFR at Week 52 calculated by CKD-EPI creatinine equation | Full Analysis Population participants with available data at Week 52 | Posted | Mean | 95% Confidence Interval | mL/min/1.73 m² | Measured at Week 52 Post-transplant |
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| Secondary | The Slope of eGFR Over Time in Year 1 | The slope of eGFR over time in Year 1, calculated by CKD-EPI Creatinine equation. Slope is computed via the repeated measures analysis, covering the study time points of weeks 13, 26, 39 and 52. The estimated average slope (and corresponding 95% confidence interval) is provided for incremental progression from one time point to the next (i.e., the displayed slope shows the extent of increase (positive) or decrease (negative) in eGFR level per every time point (13 weeks) elapsed. | Participants from the Full Analysis Population with available eGFR data in Year 1. | Posted | Mean | 95% Confidence Interval | mL/min/1.73 m² per 13 weeks | Time points in Year 1 (four time points: weeks 13, 26, 39, 52) |
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| Secondary | HIV DNA in Peripheral Blood CD4+ T Cells at Week 52 | HIV DNA in peripheral blood CD4+ T cells at Week 52. The standard ACTG type extraction protocol was used to extract DNA from PBMC. The readout was copies of cellular HIV-1 DNA per million PBMC. Subsequently, the outcome measure/value was obtained by multiplying the readout by the participant's CD4 percentage level at that time point, to obtain the measure of copies of HIV-1 DNA per million peripheral blood CD4+ T cells | Full Analysis Population | Posted | Median | Inter-Quartile Range | copies of HIV-1 DNA/million CD4+ T cells | At week 52 post-transplant |
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| Secondary | HIV RNA in Peripheral Blood CD4+ T Cells at Week 52. | HIV RNA in peripheral blood CD4+ T cells at Week 52. The standard ACTG type extraction protocol was used to extract RNA from PBMC. The readout was copies of cellular HIV-1 RNA per million PBMC. Subsequently, the outcome measure/value was obtained by multiplying the readout by the participant's CD4 percentage level at that time point, to obtain the measure of copies of HIV-1 RNA per million peripheral blood CD4+ T cells | Full Analysis Population | Posted | Median | Inter-Quartile Range | copies of HIV-1 RNA/million CD4+ T cells | Week 52 Post Transplant |
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| Secondary | Plasma HIV RNA Levels (Single Copy Assay) at Week 52 | Plasma HIV RNA levels (single copy assay) at Week 52 Post-transplant | Full Analysis Population | Posted | Median | Inter-Quartile Range | copies of HIV-1 RNA/mL | Week 52 Post-transplant |
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| Secondary | Cumulative Incidence/Proportion of Biopsy Proven Acute Rejection Within 1 Year Post Transplant | Defined by histologic evidence of rejection and graft dysfunction as identified on central read of biopsy slides as well as on site biopsies. When a central read of biopsy slide is available, those results will be used; in its absence, site biopsy result will be used. Both acute cellular and humoral rejections were considered for this outcome measure, but borderline results were excluded. | Full Analysis Population | Posted | Number | 95% Confidence Interval | Proportion of participants | Within Year 1 Post-transplant |
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| Secondary | Cumulative Incidence/Proportion of Acute Cellular Rejection Grade Equal to or Greater Than 1A During the Entire Study Follow-up | Measured by the Banff 2007 criteria as identified on central read of biopsy slides; for site biopsy results, grading was not available, all results except for borderline results were assumed to be grade 1A or greater. If available, central read result was used; if not, site biopsy result was used. | Full Analysis Population | Posted | Number | 95% Confidence Interval | Proportion of participants | Within 3 years post-transplant |
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| Secondary | Incidence/Proportion of Antibody Mediated Rejection | Incidence of humoral/antibody mediated rejection within 52 weeks of the transplant. Both central reads and site biopsy results were included, and central read result was used if one was available, and if not, the site biopsy result was used. | Full Analysis Population | Posted | Number | 95% Confidence Interval | Proportion of participants | Within 52 weeks post transplant |
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| Secondary | Proportion of Participants With de Novo Anti-donor Human Leukocyte Antigen (HLA) Antibodies | Proportion of participants with de novo anti-donor human leukocyte antigen (HLA) antibodies at Week 52 | Full Analysis Population with participants contributing data to week 52 time point | Posted | Number | 95% Confidence Interval | Proportion of participants | Measured at Week 52 |
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| Secondary | Incidence/Proportion of Participants With HIV Infection in the Renal Allograft | Histology/in situ hybridization was used to assess HIV infection in the renal allograft and calculate the proportion of participants with HIV infection | Full Analysis Population | Posted | Number | 95% Confidence Interval | Proportion of participants | Month 6 Post-transplant |
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| Secondary | Incidence of Death at Year 1 | Incidence of death within Year 1 post-transplant | Full Analysis Population | Posted | Number | 95% Confidence Interval | Percent (KM estimate for incidence) | Within Year 1 Post-transplant |
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| Secondary | Incidence of Graft Loss in Year 1 | Incidence of graft loss within Year 1 post-transplant. | Full Analysis Population | Posted | Number | 95% Confidence Interval | Percent (KM estimate for incidence) | Within Year 1 Post-transplant |
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| Secondary | Incidence of All Adverse Events (AEs) Greater Than or Equal to Grade 3 at Year 1 | Incidence of all adverse events (AEs) greater than or equal to Grade 3 within 1 year post-transplant | Full Analysis Population | Posted | Number | 95% Confidence Interval | Percent (KM estimate for incidence) | Within Year 1 Post-transplant |
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| Secondary | Incidence of Serious Adverse Events (SAEs) Greater Than or Equal to Grade 3 Within Year 1 | Incidence of serious adverse events (SAEs) greater than or equal to Grade 3 within 1 year post-transplant | Full Analysis Population | Posted | Number | 95% Confidence Interval | Percent (KM estimate for incidence) | Within Year 1 Post-transplant |
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| Secondary | Incidence of Opportunistic Infections or Neoplasms Within Year 1 | Incidence of opportunistic infections or neoplasms within 1 year post-transplant | Full Analysis Population | Posted | Number | 95% Confidence Interval | Percent (KM estimate for incidence) | Within Year 1 Post-transplant |
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| Secondary | Incidence of Non-opportunistic Infections Requiring Hospitalization Within Year 1 | Incidence of non-opportunistic infections requiring hospitalization within 1 year post-transplant | Full Analysis Population | Posted | Number | 95% Confidence Interval | Percent (KM estimate for incidence) | Within Year 1 Post-transplant |
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| Secondary | Calcineurin Inhibitor (Tacrolimus) Trough Levels for Participants on Maraviroc Versus Placebo | Calcineurin inhibitor (tacrolimus) trough levels, from 0-12 hours post-dose at month 3 post-transplant for a subset of participants enrolled at UCSF | PK Analysis Population: Subset of Participants Enrolled at UCSF | Posted | Median | Inter-Quartile Range | nM | Month 3 Post-transplant (0-12 hours post-dose) |
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| Secondary | Calcineurin Inhibitor (Tacrolimus) AUC for Participants on Maraviroc Versus Placebo | Calcineurin inhibitor (tacrolimus) AUC, 0-12 hours post-dose at month 3 post-transplant for a subset of participants enrolled at UCSF | PK Analysis Population: Subset of participants enrolled at UCSF | Posted | Median | Inter-Quartile Range | nmol-h/L | Month 3 Post-transplant (0-12 hours post-dose) |
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| Secondary | AUC of CCR5 Blockade (Maraviroc) | AUC of CCR5 blockade (maraviroc), 0-12 hours post-dose at month 3 post-transplant in a subset of participants enrolled at UCSF | PK Analysis Population: Maraviroc recipients in a subset of participants enrolled at UCSF | Posted | Median | Inter-Quartile Range | nmol-h/L | Month 3 Post-transplant (0-12 hours post-dose) |
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| Secondary | Trough Levels of CCR5 Blockade (Maraviroc) | Trough levels of CCR5 blockade (maraviroc) from 0-12 hours post-dose testing at month 3 post-transplant in a subset of participants enrolled at UCSF | PK Analysis Population: Maraviroc recipients in a subset of participants enrolled at UCSF | Posted | Median | Inter-Quartile Range | nM | Month 3 Post-transplant (0-12 hours post-dose) |
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Adverse events were collected during the study follow-up period of up to ~ 3 years post-transplant. Adverse events will be collected from the time of transplant until a participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.
Clinicaltrials.gov definitions of AEs were followed. Only grade 3 or higher AEs were required to be recorded in the database. However, all cases of the following should be recorded, regardless of grade:
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1: Maraviroc (MVC) | Participants who were assigned to and received Maraviroc in the study. | 5 | 49 | 37 | 49 | 28 | 49 |
| EG001 | Arm 2: Placebo | Participants who were assigned to and received Placebo in the study. | 3 | 48 | 34 | 48 | 37 | 48 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
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| Thrombotic microangiopathy | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Gastrointestinal motility disorder | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Ileal perforation | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Retroperitoneal effusion | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Impaired healing | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
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| Anaphylactic reaction | Immune system disorders | MedDRA 25.0 | Systematic Assessment |
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| Kidney transplant rejection | Immune system disorders | MedDRA 25.0 | Systematic Assessment |
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| Transplant rejection | Immune system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Abdominal abscess | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Arthritis infective | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Atypical pneumonia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Cytomegalovirus viraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Diabetic foot infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Enterococcal bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Gastroenteritis cryptosporidial | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Gastroenteritis shigella | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Mycotic endophthalmitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Neurosyphilis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Perirectal abscess | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Peritonitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Postoperative wound infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Primary syphilis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Pyelonephritis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Renal graft infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Syphilis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Tooth abscess | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Complications of transplanted kidney | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| Delayed graft function | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| Graft loss | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| Postoperative ileus | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| Product administration interrupted | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| SARS-CoV-2 test positive | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypervolaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypovolaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Lactic acidosis | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Mucoepidermoid carcinoma of salivary gland | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.0 | Systematic Assessment |
| |
| Tonsil cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.0 | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Anuria | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Perinephric collection | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Subcapsular renal haematoma | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pulmonary cavitation | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Diabetic bullosis | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Diabetic foot | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pancreas transplant | Surgical and medical procedures | MedDRA 25.0 | Systematic Assessment |
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| Arteriovenous fistula | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypertensive crisis | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypertensive urgency | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Iliac artery dissection | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Transplant rejection | Immune system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Pyelonephritis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Glomerular filtration rate abnormal | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
For the primary outcome "measured GFR by iohexol clearance at week 52", only 30 subjects (vs. 130 planned) could complete the on-site iohexol study due to COVID-19 restrictions and contribute data. There were also consistency/reliability issues with the generated data due to varying laboratory controls. Secondary outcome of "Mean eGFR at Week 52 Based on CKD-EPI Creatinine Equation" is a good surrogate for the primary outcome, with better reliability and bigger sample size for group comparison.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Research Manager | University of California, San Francisco | 415-595-1226 | Rodney.Rogers@ucsf.edu |
| Jun 7, 2023 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 28, 2019 | Apr 27, 2023 | ICF_001.pdf |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D007674 | Kidney Diseases |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077592 | Maraviroc |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Black or African American |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Unknown/ Not Reported |
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| Other |
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