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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00006412
First received: October 13, 2000
Last updated: July 19, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
HIV Infections
Lipodystrophy
Drug: Pravastatin sodium
Drug: Fenofibrate
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: A Prospective, Multicenter, Randomized Trial Comparing the Efficacy and Safety of Fenofibrate Versus Pravastatin in HIV-Infected Subjects With Lipid Abnormalities

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 630
Study Completion Date: May 2003
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.]

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006412

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
UCLA CARE Ctr
Los Angeles, California, United States, 90095
Willow Clinic
Menlo Park, California, United States, 94025
Univ of California, San Diego
San Diego, California, United States, 92103
University of California San Francisco
San Francisco, California, United States, 941104206
Univ of California San Francisco
San Francisco, California, United States, 94110
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
Harbor UCLA Med Ctr
Torrance, California, United States, 90502
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
Denver Dept of Health and Hosps
Denver, Colorado, United States, 80262
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Georgia
Emory Univ
Atlanta, Georgia, United States, 30308
United States, Hawaii
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
Tripler Army Med Ctr
Tripler AMC, Hawaii, United States, 96859
United States, Illinois
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
The CORE Ctr
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States, 46202
Wishard Hosp
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
Boston Med Ctr
Boston, Massachusetts, United States, 02118
Brigham and Women's Hosp
Boston, Massachusetts, United States, 02215
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Nebraska
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
United States, New York
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Mount Sinai Med Ctr
New York, New York, United States, 10029
Cornell Univ Med Ctr
New York, New York, United States, 10021
Beth Israel Med Ctr
New York, New York, United States, 10003
Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
Cornell Clinical Trials Unit - Chelsea Clinic
New York, New York, United States, 10011
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
St Mary's Hosp (Univ of Rochester/Infectious Diseases)
Rochester, New York, United States, 14642
Community Health Network Inc
Rochester, New York, United States, 14642
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Carolinas Med Ctr
Charlotte, North Carolina, United States, 28203
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
Moses H Cone Memorial Hosp
Greensboro, North Carolina, United States, 27401
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
MetroHealth Med Ctr
Cleveland, Ohio, United States, 441091998
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
United States, Pennsylvania
Philadelphia Veterans Administration Med Ctr
Philadelphia, Pennsylvania, United States, 19104
Univ of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Univ of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Miriam Hosp / Brown Univ
Providence, Rhode Island, United States, 02906
Rhode Island Hosp / Brown Univ
Providence, Rhode Island, United States, 02903
Brown Univ / Miriam Hosp
Providence, Rhode Island, United States, 02906
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Tennessee
Vanderbilt Univ Med Ctr
Nashville, Tennessee, United States, 37203
United States, Texas
Univ of Texas, Southwestern Med Ctr of Dallas
Dallas, Texas, United States, 75390
Univ of Texas Galveston
Galveston, Texas, United States, 775550435
United States, Washington
Univ of Washington
Seattle, Washington, United States, 98104
Puerto Rico
Univ of Puerto Rico
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Investigators
Study Chair: Judith Aberg
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00006412     History of Changes
Other Study ID Numbers: A5087, 10917, ACTG A5087, AACTG A5087
Study First Received: October 13, 2000
Last Updated: July 19, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Hyperlipidemia
Procetofen
Pravastatin
Antilipemic Agents

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lipodystrophy
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Fenofibrate
Pravastatin
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014