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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00006412

Collaborator

(none)

630

Enrollment

Locations

10.9

Patients Per Site

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections Lipodystrophy	Drug: Pravastatin sodium Drug: Fenofibrate	Phase 3

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.]

Study Design

Study Type:

Interventional

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

Actual Study Completion Date :

May 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California	United States	900331079
3	UCLA CARE Ctr	Los Angeles	California	United States	90095
4	Willow Clinic	Menlo Park	California	United States	94025
5	Univ of California, San Diego	San Diego	California	United States	92103
6	University of California San Francisco	San Francisco	California	United States	941104206
7	Univ of California San Francisco	San Francisco	California	United States	94110
8	San Mateo AIDS Program / Stanford Univ	Stanford	California	United States	943055107
9	Stanford Univ Med Ctr	Stanford	California	United States	943055107
10	Harbor UCLA Med Ctr	Torrance	California	United States	90502
11	Denver Dept of Health and Hosps	Denver	Colorado	United States	80262
12	Univ of Colorado Health Sciences Ctr	Denver	Colorado	United States	80262
13	Univ of Miami School of Medicine	Miami	Florida	United States	331361013
14	Emory Univ	Atlanta	Georgia	United States	30308
15	Univ of Hawaii	Honolulu	Hawaii	United States	96816
16	Tripler Army Med Ctr	Tripler AMC	Hawaii	United States	96859
17	Northwestern Univ Med School	Chicago	Illinois	United States	60611
18	The CORE Ctr	Chicago	Illinois	United States	60612
19	Indiana Univ Hosp	Indianapolis	Indiana	United States	462025250
20	Methodist Hosp of Indiana / Life Care Clinic	Indianapolis	Indiana	United States	46202
21	Wishard Hosp	Indianapolis	Indiana	United States	46202
22	Johns Hopkins Hosp	Baltimore	Maryland	United States	21287
23	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts	United States	02114
24	Boston Med Ctr	Boston	Massachusetts	United States	02118
25	Beth Israel Deaconess - West Campus	Boston	Massachusetts	United States	02215
26	Brigham and Women's Hosp	Boston	Massachusetts	United States	02215
27	Univ of Minnesota	Minneapolis	Minnesota	United States	55455
28	Univ of Nebraska Med Ctr	Omaha	Nebraska	United States	681985130
29	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York	United States	14215
30	Beth Israel Med Ctr	New York	New York	United States	10003
31	Cornell Clinical Trials Unit - Chelsea Clinic	New York	New York	United States	10011
32	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
33	Cornell Univ Med Ctr	New York	New York	United States	10021
34	Mount Sinai Med Ctr	New York	New York	United States	10029
35	Columbia Presbyterian Med Ctr	New York	New York	United States	10032
36	Community Health Network Inc	Rochester	New York	United States	14642
37	St Mary's Hosp (Univ of Rochester/Infectious Diseases)	Rochester	New York	United States	14642
38	Univ of Rochester Medical Center	Rochester	New York	United States	14642
39	Univ of North Carolina	Chapel Hill	North Carolina	United States	275997215
40	Carolinas Med Ctr	Charlotte	North Carolina	United States	28203
41	Duke Univ Med Ctr	Durham	North Carolina	United States	27710
42	Moses H Cone Memorial Hosp	Greensboro	North Carolina	United States	27401
43	Univ of Cincinnati	Cincinnati	Ohio	United States	452670405
44	Case Western Reserve Univ	Cleveland	Ohio	United States	44106
45	MetroHealth Med Ctr	Cleveland	Ohio	United States	441091998
46	Ohio State Univ Hosp Clinic	Columbus	Ohio	United States	432101228
47	Philadelphia Veterans Administration Med Ctr	Philadelphia	Pennsylvania	United States	19104
48	Univ of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
49	Univ of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
50	Rhode Island Hosp / Brown Univ	Providence	Rhode Island	United States	02903
51	Brown Univ / Miriam Hosp	Providence	Rhode Island	United States	02906
52	Miriam Hosp / Brown Univ	Providence	Rhode Island	United States	02906
53	Julio Arroyo	West Columbia	South Carolina	United States	29169
54	Vanderbilt Univ Med Ctr	Nashville	Tennessee	United States	37203
55	Univ of Texas, Southwestern Med Ctr of Dallas	Dallas	Texas	United States	75390
56	Univ of Texas Galveston	Galveston	Texas	United States	775550435
57	Univ of Washington	Seattle	Washington	United States	98104
58	Univ of Puerto Rico	San Juan		Puerto Rico	009365067