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Optimal Treatment for Kidney Disease in HIV Infected Adults

Primary Purpose

HIV Infections, Kidney Disease

Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Valsartan
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Treatment Experienced

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: HIV infected Evidence of HIV-associated nephropathy by kidney biopsy performed locally within 24 weeks prior to study entry On ART for at least 42 days prior to study entry and willing to continue ART while on study Systolic blood pressure (BP) between 91 mm Hg and 170 mm Hg and diastolic BP 105 mm Hg or less within 24 hours of study entry Stable kidney function, as indicated by two consecutive calculated creatinine clearance measurements higher than 30 ml/min Serum potassium of less than Grade 1 within 7 days prior to study entry Willing to follow dose adjustments of non-study antihypertensive drugs if necessary Willing to use acceptable forms of contraception Exclusion Criteria: Current treatment with hemodialysis or peritoneal dialysis History of kidney transplant Condition other than HIVAN contributing to decreased kidney function ALT or AST greater than 5 times the upper limit of normal (ULN) within 28 days of study entry Total bilirubin greater than 2.5 times ULN within 28 days of study entry. Patients with total bilirubin between 2.5 times and 5 times ULN who are receiving indinavir or atazanavir and do not have cirrhosis or severe liver disease are not excluded. Current heart indication for an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) Use of an ACEI or ARB within 7 days prior to first creatinine clearance measurement obtained for screening or any time between screening and study entry Systemic steroid therapy above a replacement level within 28 days of study entry, or possible need for ongoing systemic steroid therapy above replacement level during the study Current use of cimetidine Use of investigational agents, except when approved by the protocol chairs Allergy or sensitivity to valsartan or its formulations Blood pressure not measurable by the technique described in the protocol Orthostatic drop in systolic BP of 30 mm Hg or more within 24 hours prior to study entry Drug or alcohol use that, in the opinion of the investigator, would interfere with the study Decreased mental capacity that, in the opinion of the investigator, would interfere with the study AIDS-defining opportunistic infection (OI) within 28 days prior to study entry. Patients who are receiving maintenance therapy for OIs and have no evidence of active disease are not excluded. Diabetes mellitus for 2 years or longer prior to study entry. Onset of diabetes is defined as the point at which patients began oral hypoglycemics or insulin. Pregnancy or breastfeeding

Sites / Locations

  • Indiana University Hospital
  • Methodist Hospital of Indiana
  • Wishard Hospital
  • Washington University (St. Louis)
  • NYU/Bellevue
  • Duke University Medical Center
  • MetroHealth Medical Center
  • Rhode Island Hospital
  • Stanley Street Treatment and Resource
  • The Miriam Hospital

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
August 5, 2004
Last Updated
March 5, 2015
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00089518
Brief Title
Optimal Treatment for Kidney Disease in HIV Infected Adults
Official Title
A Phase III, Randomized, Placebo-Controlled, Double-Blind Trial of an Angiotensin Receptor Blocker (Valsartan) and Highly Active Antiretroviral Therapy (HAART) Versus HAART Alone for the Treatment of HIV-Associated Nephropathy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2009
Overall Recruitment Status
Withdrawn
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
The angiotensin receptor blocker (ARB) valsartan is a drug commonly used to treat high blood pressure. Valsartan may also help slow down the progression of kidney disease in HIV infected people. The purpose of this study is to compare valsartan and antiretroviral therapy (ART) to ART alone in slowing kidney disease progression in people with HIV.
Detailed Description
ART for the treatment of HIV may slow the progression of HIV-associated nephropathy (HIVAN) to end-stage renal disease (ESRD); nevertheless, it is predicted that many HIV infected patients on ART will reach ESRD by the next decade. Medications that affect the renin-angiotensin system, such as the ARB valsartan, may be useful in treating HIVAN. In a small study of HIV infected patients with HIVAN treated with the angiotensin-converting enzyme inhibitor (ACEI) fosinopril, kidney function was stable in patients who took the ACEI, but function decreased in patients who did not. These data are promising, and suggest that an ARB like valsartan may also slow the progression of HIVAN and improve patients' prognosis. This study will compare valsartan and ART to ART alone in slowing kidney disease progression in people with HIV. This study will last 96 weeks. All participants will continue taking their current ART regimen during the study and will be randomly assigned to one of two arms: Arm 1 will receive valsartan daily, while Arm 2 will receive placebo daily. Doses of drug or placebo may be adjusted during the first 8 weeks based on blood pressure readings taken during the study. In addition, if patients are on other antihypertensive drugs, dosage adjustments may be necessary for those drugs during the study. No ART or antihypertensive drugs other than valsartan will be provided by the study. Study visits will occur every week until Week 8, then every 8 weeks until the end of the study at Week 96. Study visits will include physical examination, medication assessment, and blood pressure readings. In addition, blood collection will occur at entry, Weeks 2, 4, 6, and 8, and every 8 weeks thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Kidney Disease
Keywords
Treatment Experienced

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Valsartan

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: HIV infected Evidence of HIV-associated nephropathy by kidney biopsy performed locally within 24 weeks prior to study entry On ART for at least 42 days prior to study entry and willing to continue ART while on study Systolic blood pressure (BP) between 91 mm Hg and 170 mm Hg and diastolic BP 105 mm Hg or less within 24 hours of study entry Stable kidney function, as indicated by two consecutive calculated creatinine clearance measurements higher than 30 ml/min Serum potassium of less than Grade 1 within 7 days prior to study entry Willing to follow dose adjustments of non-study antihypertensive drugs if necessary Willing to use acceptable forms of contraception Exclusion Criteria: Current treatment with hemodialysis or peritoneal dialysis History of kidney transplant Condition other than HIVAN contributing to decreased kidney function ALT or AST greater than 5 times the upper limit of normal (ULN) within 28 days of study entry Total bilirubin greater than 2.5 times ULN within 28 days of study entry. Patients with total bilirubin between 2.5 times and 5 times ULN who are receiving indinavir or atazanavir and do not have cirrhosis or severe liver disease are not excluded. Current heart indication for an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) Use of an ACEI or ARB within 7 days prior to first creatinine clearance measurement obtained for screening or any time between screening and study entry Systemic steroid therapy above a replacement level within 28 days of study entry, or possible need for ongoing systemic steroid therapy above replacement level during the study Current use of cimetidine Use of investigational agents, except when approved by the protocol chairs Allergy or sensitivity to valsartan or its formulations Blood pressure not measurable by the technique described in the protocol Orthostatic drop in systolic BP of 30 mm Hg or more within 24 hours prior to study entry Drug or alcohol use that, in the opinion of the investigator, would interfere with the study Decreased mental capacity that, in the opinion of the investigator, would interfere with the study AIDS-defining opportunistic infection (OI) within 28 days prior to study entry. Patients who are receiving maintenance therapy for OIs and have no evidence of active disease are not excluded. Diabetes mellitus for 2 years or longer prior to study entry. Onset of diabetes is defined as the point at which patients began oral hypoglycemics or insulin. Pregnancy or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lynda Anne Szczech, MD, MSCE
Organizational Affiliation
Division of Nephrology, Department of Medicine, Duke University Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Indiana University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5250
Country
United States
Facility Name
Methodist Hospital of Indiana
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5250
Country
United States
Facility Name
Wishard Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Washington University (St. Louis)
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63108-2138
Country
United States
Facility Name
NYU/Bellevue
City
New York
State/Province
New York
ZIP/Postal Code
10016-6481
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
MetroHealth Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109-1998
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
Stanley Street Treatment and Resource
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
The Miriam Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
12704580
Citation
Herman ES, Klotman PE. HIV-associated nephropathy: Epidemiology, pathogenesis, and treatment. Semin Nephrol. 2003 Mar;23(2):200-8. doi: 10.1053/snep.2003.50018.
Results Reference
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PubMed Identifier
12899589
Citation
Kimmel PL, Barisoni L, Kopp JB. Pathogenesis and treatment of HIV-associated renal diseases: lessons from clinical and animal studies, molecular pathologic correlations, and genetic investigations. Ann Intern Med. 2003 Aug 5;139(3):214-26.
Results Reference
background
PubMed Identifier
11984599
Citation
Marras D, Bruggeman LA, Gao F, Tanji N, Mansukhani MM, Cara A, Ross MD, Gusella GL, Benson G, D'Agati VD, Hahn BH, Klotman ME, Klotman PE. Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy. Nat Med. 2002 May;8(5):522-6. doi: 10.1038/nm0502-522.
Results Reference
background
PubMed Identifier
12969167
Citation
Wei A, Burns GC, Williams BA, Mohammed NB, Visintainer P, Sivak SL. Long-term renal survival in HIV-associated nephropathy with angiotensin-converting enzyme inhibition. Kidney Int. 2003 Oct;64(4):1462-71. doi: 10.1046/j.1523-1755.2003.00230.x.
Results Reference
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Optimal Treatment for Kidney Disease in HIV Infected Adults

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