Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201711002808414 Date of Approval: 27/11/2017
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Optimal Management of HIV-Infected Adults at Risk for Kidney Complications in Nigeria (R3 Study)
Official scientific title Optimal Management of HIV-Infected Adults at Risk for Kidney Complications in Nigeria
Brief summary describing the background and objectives of the trial Individuals of African descent have a much higher risk for glomerular diseases. Specifically, persons possessing two copies of the risk variants in the APOL1 gene, referred to as the high-risk (HR) genotype, are at high risk for non-diabetic kidney disease. The presence of these risk variants is highest in West Africa, specifically in Nigeria, where ~50% of HIV-positive individuals carrying the APOL1 HR genotype will develop chronic kidney disease (CKD). As availability of dialysis and kidney transplantation in Nigeria is limited, most individuals die soon after developing end-stage kidney disease (ESKD). Markers of kidney disease include microalbuminuria, proteinuria, and/or reduced estimated glomerular filtration rate (eGFR), all three of which are associated with increased mortality in HIV+ adults. Increased urinary albumin excretion has diagnostic and prognostic value in the identification and confirmation of renal disease, and changes in albuminuria can be useful in assessing treatment efficacy and disease progression. The renin-angiotensin aldosterone system (RAAS) is the central player in the pathophysiology of CKD, and blocking RAAS with angiotensin converting enzyme inhibitors (ACEi) is a recognized strategy to slow or halt renal disease progression in diabetics with CKD. We will therefore enroll HIV+ ART-experienced adults in Nigeria to: 1) determine the prevalence of APOL1 renal risk variants and assess whether APOL1 HR status correlates with prevalent albuminuria, eGFR, and/or prevalent CKD; 2) assess whether RAAS inhibition (with the ACEi lisinopril) in addition to ART, compared to the existing standard-of-care (SOC), significantly reduces the incidence of additional kidney disease manifestations; and 3) determine whether the APOL1 HR genotype is associated with worse longitudinal renal outcomes in Nigerians with prevalent albuminuria.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations,Kidney Disease,Kidney Diseases, Albuminuria, Genetic Predisposition
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Other
Anticipated trial start date 01/11/2017
Actual trial start date 13/09/2018
Anticipated date of last follow up 28/02/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 280
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
NCT03201939 Clinical Trials.gov
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised block randomization using baseline urinary albumin creatinine ratios (30-100 mg/g vs. 101-300 mg/g), 100 per arm allocation will be determined by off-site coordinator using study ID numbers Masking/blinding used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Lisinopril 10-40mg, daily 2 - 2.5 years oral tablet, overencapsulated 140 Placebo
Control Group placebo 1- 2 tablets, daily 2 - 2.5 years oral tablet, overencapsulated 140 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Adult (18-70 years of age) Documented positive HIV-1 ELISA On ART for a minimum of 6 months, suppresses plasma viral load result (<20 copies/mL) with past six months Average uACR between 30-300 mg/g (based on 2 uACRs [first morning voids], with the second obtained 4-8 weeks after first specimen) Urine dipstick proteinuria analysis result <2.0 eGFR = > 60ml/min/1.73m2 (using CKD-EPI-Cr-CYC equation) If female, non pregnant (documentation of negative urine pregnancy test ) and not breastfeeding/lactating • K+ >5.0 meEq/L or reasons to be concerned about hyperkalemia • Known history of diabetes mellitus (would qualify for treatment with an ACEi/ARB) • Poorly controlled hypertension (≥3 BP readings >160/110 in past 6 months) • Known history of congestive heart failure (chronic) • Average uACR (calculated on values obtained from 2 successive measures 4-8 weeks apart) of < 30 mg/g OR > 300 mg/g • Relative symptomatic hypotension (BP <90/60) • Currently receiving an ACEi and/or ARB; • Lack of suitability as a study candidate (i.e. active substance use disorder, active use of potentially nephrotoxic medication(s) (i.e. traditional medicines, etc.) and/or history of poor compliance (i.e. multiple missed scheduled clinic appointments, etc.) Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 70 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 18/10/2017 Research Ethics Committee, Aminu Kano Teaching Hospital
Ethics Committee Address
Street address City Postal code Country
PMB 3452, Zaria Road Kano Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 16/08/2018 Vanderbilt University Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
1313 21st Ave South, Suite 504 Nashville 37232 United States of America
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Regression from microalbuminuria (uACR 30-300) to normoalbuminuria (uACR < 30 mg/g) by study arm Timeframe 2 years month 3 month 6 month 9 month 12 month 15 month 18 month 24
Primary Outcome Progression from microalbuminuria (uACR 30-300) to macroalbuminuria (uACR > 300 mg/g) by study arm [ Time Frame: 2 years ] month 3 month 6 month 9 month 12 month 15 month 18 month 24
Secondary Outcome Mean change in urinary albumin to creatinine ration (uACR) month 3 month 6 month 9 month 12 month 15 month 18 month 24
Secondary Outcome doubling of serum creatinine from baseline month 3 month 6 month 9 month 12 month 15 month 18 month 24
Secondary Outcome All-cause mortality [ Time Frame: 2 years ] throughout study
Primary Outcome Mean change in urinary albumin to creatinine ratio (uACR) [ Time Frame: 2 years ] Month 3 month 6 month 12, month 15 month 18 month 24
Secondary Outcome Doubling of serum creatinine from baseline [ Time Frame: 2 years ] Throughout sutdy
Secondary Outcome Proportion experiencing a 40% decline in eGFR [ Time Frame: 2 years ] Throughout study
Secondary Outcome Mean change in eGFR over time [ Time Frame: 2 years ] Throughout study
Secondary Outcome Change in clinical/performance status as ascertained via World Health Organization Quality of Life HIV (WHOQOL-HIV) scale Time Frame: baseline, 1 year, 2 years
Primary Outcome Change in clinical/performance status as ascertained via Karnofsky Performance Score Time Frame: baseline, 1 year, 2 years
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Aminu Kano Teaching Hospital PMB 3452, Zaria Rd Kano Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institutes of Health 9000 Rockville Pike Bethesda 20892 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Vanderbilt University Medical Center 1211 Medical Center Drive Nashville 37232 United States of America Hospital
COLLABORATORS
Name Street address City Postal code Country
C. William Wester 2525 West End Ave, Suite 750 Nashville 37203 United States of America
Muktar Aliyu 2525 West End Ave, Suite 750 Nashville 37203 United States of America
Baba M. Musa PMB 3452, Zaria Rd Kano Nigeria
Aliyu Abdu PMB 3452, Zaria Rd Kano Nigeria
Aisha M. Nalado PMB 3452, Zaria Rd Kano Nigeria
Mahmoud U. Sani PMB 3452, Zaria Rd Kano Nigeria
Muhammad Hamza PMB 3452, Zaria Rd Kano Nigeria
Akinfenwa Atanda PMB 3452, Zaria Rd Kano Nigeria
Bryan E. Shepherd 2525 West End Ave, Suite 11000 Nashville 37203 United States of America
Aima Ahonkhai 2525 West End Ave, Suite 750 Nashville 37203 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator C. William Wester william.wester@vanderbilt.edu 6158750145 2525 West End Ave, Suite 750
City Postal code Country Position/Affiliation
Nashville 37203 United States of America Associate Professor of Medicine
Role Name Email Phone Street address
Principal Investigator Muktar Aliyu muktar.aliyu@vanderbilt.edu 615-343-2418 2525 West End Ave, Suite 750
City Postal code Country Position/Affiliation
Nashville 37203 United States of America Associate Professor of Medicine
Role Name Email Phone Street address
Public Enquiries Donna Ingles donna.j.ingles@vanderbilt.edu 6153433555 2525 West End Ave, Suite 750
City Postal code Country Position/Affiliation
Nashville 37203 United States of America Senior Program Manager, Institute for Global Health
Role Name Email Phone Street address
Scientific Enquiries Donna Ingles donna.j.ingles@vanderbilt.edu 6153433555 2525 West End Ave, Suite 750
City Postal code Country Position/Affiliation
Nashville 37203 United States of America Senior Program Manager, Institute for Global Health
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Undecided
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information