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Safety and Effectiveness of Fenofibrate and Pravastatin in HIV-Positive Patients With Abnormal Blood Lipids

Primary Purpose

HIV Infections, Lipodystrophy

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Pravastatin sodium
Fenofibrate
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 Hyperlipidemia, Procetofen, Pravastatin, Antilipemic Agents

Eligibility Criteria

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

Inclusion Criteria Patients may be eligible for this study if they: Are HIV-positive. Are at least 18 years old. Are on a lipid-lowering diet based on the patient's statement and have been exercising for at least 30 days before being screened for the study. Patients will be asked if they were counseled by their health care provider. The lipid-lowering diet and exercise program do not have to be prescribed by a physician. Have a triglyceride (TG) level of at least 200 mg/dl and low-density lipoprotein (LDL) level of at least 130 mg/dl after fasting for 8 to 12 hours. Have been treated with anti-HIV drugs for more than 6 months. Patients must be taking the anti-HIV drugs regularly for at least 4 weeks before they enter the study. Patients must be taking anti-HIV drugs regularly for at least 8 weeks if they have changed from taking protease inhibitor (PI) anti-HIV drugs to non-PI anti-HIV drugs. Any combination without a PI must lower the patient's HIV viral levels, as determined by the patient's physician. Are willing, if able to become pregnant, to use 2 reliable types of birth control while taking the study drug(s) and for 1 month after stopping the drug(s). Have a negative pregnancy test. (This reflects a change in inclusion requirements.) Exclusion Criteria Patients will not be eligible for the study if they: Have a history of heart disease. Have uncontrolled high blood pressure within 4 weeks of study entry. Have liver disease. Have gall bladder disease or symptoms within 3 months prior to study entry or symptoms of gallstones. Had surgery to remove their gallbladder within 3 months prior to study entry. Have diabetes requiring drug treatment or diabetes not controlled by diet. Have hypothyroidism (low thyroid activity). Are allergic or sensitive to the study drug(s) or to other lipid-lowering drugs. Have rhabdomyolysis (a muscle disease). Have taken any prescription or non-prescription lipid-lowering drug within 14 days prior to study entry or for over 24 weeks in the past. Take prescription lipid-lowering agents, other than those given by the study, and non-prescription lipid-lowering agents such as garlic supplements. Have failed previous statin or fibrate therapy (after 24 weeks of treatment) or have had side effects from these drugs. Receive or have received (within 14 days of study entry) treatment not approved by the FDA. Anti-HIV medications and immune-based treatments not approved by the FDA may be allowed on a case-by-case basis with the approval of the protocol team. Were given systemic chemotherapy for cancer other than Kaposi's sarcoma (KS). Were given radiation therapy within 30 days of study entry. Take drugs that increase risk of muscle disease (such as cyclosporine, erythromycin, itraconazole, and ketoconazole), within 14 days of study entry. Take or have taken levothyroxine and liothyronine for hypothyroidism. Take high doses of testosterone. Take creatine monophosphate or drugs that affect the immune system, within 30 days of study entry. Abuse drugs or alcohol, and the doctor thinks this may interfere with the study. Are pregnant or breast-feeding. Had a scheduled anti-HIV treatment withdrawal prior to study entry. (This reflects a change in exclusion requirements.)

Sites / Locations

  • Univ of Alabama at Birmingham
  • Univ of Southern California / LA County USC Med Ctr
  • UCLA CARE Ctr
  • Willow Clinic
  • Univ of California, San Diego
  • University of California San Francisco
  • Univ of California San Francisco
  • San Mateo AIDS Program / Stanford Univ
  • Stanford Univ Med Ctr
  • Harbor UCLA Med Ctr
  • Denver Dept of Health and Hosps
  • Univ of Colorado Health Sciences Ctr
  • Univ of Miami School of Medicine
  • Emory Univ
  • Univ of Hawaii
  • Tripler Army Med Ctr
  • Northwestern Univ Med School
  • The CORE Ctr
  • Indiana Univ Hosp
  • Methodist Hosp of Indiana / Life Care Clinic
  • Wishard Hosp
  • Johns Hopkins Hosp
  • Harvard (Massachusetts Gen Hosp)
  • Boston Med Ctr
  • Beth Israel Deaconess - West Campus
  • Brigham and Women's Hosp
  • Univ of Minnesota
  • Univ of Nebraska Med Ctr
  • SUNY / Erie County Med Ctr at Buffalo
  • Beth Israel Med Ctr
  • Cornell Clinical Trials Unit - Chelsea Clinic
  • Bellevue Hosp / New York Univ Med Ctr
  • Cornell Univ Med Ctr
  • Mount Sinai Med Ctr
  • Columbia Presbyterian Med Ctr
  • Community Health Network Inc
  • St Mary's Hosp (Univ of Rochester/Infectious Diseases)
  • Univ of Rochester Medical Center
  • Univ of North Carolina
  • Carolinas Med Ctr
  • Duke Univ Med Ctr
  • Moses H Cone Memorial Hosp
  • Univ of Cincinnati
  • Case Western Reserve Univ
  • MetroHealth Med Ctr
  • Ohio State Univ Hosp Clinic
  • Philadelphia Veterans Administration Med Ctr
  • Univ of Pennsylvania
  • Univ of Pittsburgh
  • Rhode Island Hosp / Brown Univ
  • Brown Univ / Miriam Hosp
  • Miriam Hosp / Brown Univ
  • Julio Arroyo
  • Vanderbilt Univ Med Ctr
  • Univ of Texas, Southwestern Med Ctr of Dallas
  • Univ of Texas Galveston
  • Univ of Washington
  • Univ of Puerto Rico

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
October 13, 2000
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00006412
Brief Title
Safety and Effectiveness of Fenofibrate and Pravastatin in HIV-Positive Patients With Abnormal Blood Lipids
Official Title
A Prospective, Multicenter, Randomized Trial Comparing the Efficacy and Safety of Fenofibrate Versus Pravastatin in HIV-Infected Subjects With Lipid Abnormalities
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 2003 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to compare the safety and effectiveness of fenofibrate and pravastatin in treating HIV-positive patients who have abnormal levels of fat (lipids) in the blood. Increased lipids in the blood associated with HIV infection and anti-HIV drugs is a growing problem. The drugs used in this study are known to reduce certain lipids, but little is known about their safety and effectiveness. This study will see if one of the drugs is safer and more effective than the other, or if combining the drugs is the safest and most effective way to lower lipids. This study has been changed. On June 26, 2001, this study was reviewed by the Data and Safety Monitoring Board (DSMB). The DSMB is an independent board monitoring the progress of the study. The review showed that neither pravastatin nor fenofibrate alone were effective in reaching all the cholesterol and triglyceride goals. There were no safety concerns. It is not known if the combination of fenofibrate and pravastatin is effective and safe. Therefore, it is important to continue this study.
Detailed Description
Lipid disorders associated with HIV infection and antiretroviral therapy are of growing concern. There is little information available on the safety and efficacy of statins or fibrates in the treatment of HIV-associated hyperlipidemias. Fenofibrate and pravastatin both are able to reduce low-density lipoproteins (LDL) and triglycerides (TG), but it is unclear whether one therapy will be more effective than the other, or if combination therapy will be needed to achieve desirable reductions in both LDL and TG. [AS PER AMENDMENT 12/13/01: The NIAID HIV Therapeutic Trials Data and Safety Monitoring Board (DSMB) met June 26, 2001 to review the interim results. The interim monitoring plan for this study states that accrual into either single-agent therapy arm should stop if the response rate failed to meet a pre-specified minimum at the time of interim review. The DSMB found that this stopping criterion was met for each single-therapy arm. The DSMB recommended that patients currently on single-agent therapy be offered the opportunity to initiate dual-agent therapy, regardless of time on study. There were no safety concerns.] Patients are randomized to either Arm A or Arm B and stratified by gender, TG level, and number of cardiovascular risk factors. Patients add daily fenofibrate (Arm A) or pravastatin (Arm B) to their antiretroviral therapy for 48 weeks. Evaluations at Week 12 determine LDL, TG, and high-density lipid (HDL) levels. Patients who achieve clinical goals for these levels stay on the drug for the rest of the study. Patients who do not achieve the goals by Week 12 receive a combination of pravastatin and fenofibrate for the rest of the study. At regular clinic visits, patients have physical exams and are questioned about their medications, diet, and exercise. Blood samples are drawn for clinical evaluations, including lipid profiles and HIV-1 RNA monitoring. [AS PER AMENDMENT 12/13/01: On June 26, 2001, the DSMB reviewed interim results and determined that the response rates for both arms met the stopping rule for futility. As a result, all patients who were currently on single-agent therapy were offered the opportunity to initiate dual-agent therapy regardless of time on study. No additional accrual was sought; however, exceptions were made for patients who were in screening at the time of the DSMB review. These patients were given the option of starting single- or dual-agent therapy. The DSMB recommended that all patients on dual-agent therapy be followed for 32 weeks to obtain additional safety and efficacy data. Further endpoints will be analyzed after Week 12 of single-agent therapy or Week 32 of dual-agent therapy.]

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Lipodystrophy
Keywords
Hyperlipidemia, Procetofen, Pravastatin, Antilipemic Agents

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Enrollment
630 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Pravastatin sodium
Intervention Type
Drug
Intervention Name(s)
Fenofibrate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Patients may be eligible for this study if they: Are HIV-positive. Are at least 18 years old. Are on a lipid-lowering diet based on the patient's statement and have been exercising for at least 30 days before being screened for the study. Patients will be asked if they were counseled by their health care provider. The lipid-lowering diet and exercise program do not have to be prescribed by a physician. Have a triglyceride (TG) level of at least 200 mg/dl and low-density lipoprotein (LDL) level of at least 130 mg/dl after fasting for 8 to 12 hours. Have been treated with anti-HIV drugs for more than 6 months. Patients must be taking the anti-HIV drugs regularly for at least 4 weeks before they enter the study. Patients must be taking anti-HIV drugs regularly for at least 8 weeks if they have changed from taking protease inhibitor (PI) anti-HIV drugs to non-PI anti-HIV drugs. Any combination without a PI must lower the patient's HIV viral levels, as determined by the patient's physician. Are willing, if able to become pregnant, to use 2 reliable types of birth control while taking the study drug(s) and for 1 month after stopping the drug(s). Have a negative pregnancy test. (This reflects a change in inclusion requirements.) Exclusion Criteria Patients will not be eligible for the study if they: Have a history of heart disease. Have uncontrolled high blood pressure within 4 weeks of study entry. Have liver disease. Have gall bladder disease or symptoms within 3 months prior to study entry or symptoms of gallstones. Had surgery to remove their gallbladder within 3 months prior to study entry. Have diabetes requiring drug treatment or diabetes not controlled by diet. Have hypothyroidism (low thyroid activity). Are allergic or sensitive to the study drug(s) or to other lipid-lowering drugs. Have rhabdomyolysis (a muscle disease). Have taken any prescription or non-prescription lipid-lowering drug within 14 days prior to study entry or for over 24 weeks in the past. Take prescription lipid-lowering agents, other than those given by the study, and non-prescription lipid-lowering agents such as garlic supplements. Have failed previous statin or fibrate therapy (after 24 weeks of treatment) or have had side effects from these drugs. Receive or have received (within 14 days of study entry) treatment not approved by the FDA. Anti-HIV medications and immune-based treatments not approved by the FDA may be allowed on a case-by-case basis with the approval of the protocol team. Were given systemic chemotherapy for cancer other than Kaposi's sarcoma (KS). Were given radiation therapy within 30 days of study entry. Take drugs that increase risk of muscle disease (such as cyclosporine, erythromycin, itraconazole, and ketoconazole), within 14 days of study entry. Take or have taken levothyroxine and liothyronine for hypothyroidism. Take high doses of testosterone. Take creatine monophosphate or drugs that affect the immune system, within 30 days of study entry. Abuse drugs or alcohol, and the doctor thinks this may interfere with the study. Are pregnant or breast-feeding. Had a scheduled anti-HIV treatment withdrawal prior to study entry. (This reflects a change in exclusion requirements.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Judith Aberg
Official's Role
Study Chair
Facility Information:
Facility Name
Univ of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Univ of Southern California / LA County USC Med Ctr
City
Los Angeles
State/Province
California
ZIP/Postal Code
900331079
Country
United States
Facility Name
UCLA CARE Ctr
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Willow Clinic
City
Menlo Park
State/Province
California
ZIP/Postal Code
94025
Country
United States
Facility Name
Univ of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
941104206
Country
United States
Facility Name
Univ of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
San Mateo AIDS Program / Stanford Univ
City
Stanford
State/Province
California
ZIP/Postal Code
943055107
Country
United States
Facility Name
Stanford Univ Med Ctr
City
Stanford
State/Province
California
ZIP/Postal Code
943055107
Country
United States
Facility Name
Harbor UCLA Med Ctr
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Denver Dept of Health and Hosps
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Univ of Colorado Health Sciences Ctr
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Univ of Miami School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
331361013
Country
United States
Facility Name
Emory Univ
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Univ of Hawaii
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96816
Country
United States
Facility Name
Tripler Army Med Ctr
City
Tripler AMC
State/Province
Hawaii
ZIP/Postal Code
96859
Country
United States
Facility Name
Northwestern Univ Med School
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
The CORE Ctr
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana Univ Hosp
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
462025250
Country
United States
Facility Name
Methodist Hosp of Indiana / Life Care Clinic
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Wishard Hosp
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Johns Hopkins Hosp
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Harvard (Massachusetts Gen Hosp)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Boston Med Ctr
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Beth Israel Deaconess - West Campus
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Brigham and Women's Hosp
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Univ of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Univ of Nebraska Med Ctr
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
681985130
Country
United States
Facility Name
SUNY / Erie County Med Ctr at Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Beth Israel Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Cornell Clinical Trials Unit - Chelsea Clinic
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
Facility Name
Bellevue Hosp / New York Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cornell Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mount Sinai Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia Presbyterian Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Community Health Network Inc
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
St Mary's Hosp (Univ of Rochester/Infectious Diseases)
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Univ of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Univ of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
275997215
Country
United States
Facility Name
Carolinas Med Ctr
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Duke Univ Med Ctr
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Moses H Cone Memorial Hosp
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27401
Country
United States
Facility Name
Univ of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
452670405
Country
United States
Facility Name
Case Western Reserve Univ
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
MetroHealth Med Ctr
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
441091998
Country
United States
Facility Name
Ohio State Univ Hosp Clinic
City
Columbus
State/Province
Ohio
ZIP/Postal Code
432101228
Country
United States
Facility Name
Philadelphia Veterans Administration Med Ctr
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Univ of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Univ of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Rhode Island Hosp / Brown Univ
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Brown Univ / Miriam Hosp
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
Miriam Hosp / Brown Univ
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
Julio Arroyo
City
West Columbia
State/Province
South Carolina
ZIP/Postal Code
29169
Country
United States
Facility Name
Vanderbilt Univ Med Ctr
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Univ of Texas, Southwestern Med Ctr of Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Univ of Texas Galveston
City
Galveston
State/Province
Texas
ZIP/Postal Code
775550435
Country
United States
Facility Name
Univ of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Univ of Puerto Rico
City
San Juan
ZIP/Postal Code
009365067
Country
Puerto Rico

12. IPD Sharing Statement

Citations:
PubMed Identifier
16218799
Citation
Aberg JA, Zackin RA, Brobst SW, Evans SR, Alston BL, Henry WK, Glesby MJ, Torriani FJ, Yang Y, Owens SI, Fichtenbaum CJ; ACTG 5087 Study Team. A randomized trial of the efficacy and safety of fenofibrate versus pravastatin in HIV-infected subjects with lipid abnormalities: AIDS Clinical Trials Group Study 5087. AIDS Res Hum Retroviruses. 2005 Sep;21(9):757-67. doi: 10.1089/aid.2005.21.757.
Results Reference
result
PubMed Identifier
17434848
Citation
Evans SR, Fichtenbaum CJ, Aberg JA; A5087 Study Team. Comparison of direct and indirect measurement of LDL-C in HIV-infected individuals: ACTG 5087. HIV Clin Trials. 2007 Jan-Feb;8(1):45-52. doi: 10.1310/hct0801-45.
Results Reference
result
PubMed Identifier
20824151
Citation
Fichtenbaum CJ, Yeh TM, Evans SR, Aberg JA. Treatment with pravastatin and fenofibrate improves atherogenic lipid profiles but not inflammatory markers in ACTG 5087. J Clin Lipidol. 2010 Jul-Aug;4(4):279-87. doi: 10.1016/j.jacl.2010.04.003.
Results Reference
result

Learn more about this trial

Safety and Effectiveness of Fenofibrate and Pravastatin in HIV-Positive Patients With Abnormal Blood Lipids

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