A Study of Several Anti-HIV Drug Combinations in HIV-Infected Patients Who Have Used Indinavir

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00000892

Collaborator

(none)

300

Enrollment

Locations

6.7

Patients Per Site

Study Details

Study Description

Brief Summary

To compare the proportion of patients whose plasma HIV-1 RNA is below 500 copies/ml after 16 weeks of treatment. To assess the safety, toxicity, and tolerance of each treatment arm.

While indinavir is currently the most commonly prescribed protease inhibitor, the optimal therapy for a person on an indinavir-containing regimen who experiences a rebound in viral load or never experiences a decrease in viral load below 500 copies per milliliter is unknown. Current clinical practice for such patients typically involves empiric use of a combination of other protease inhibitors (saquinavir/nelfinavir or saquinavir/ritonavir) and at least 1 other antiretroviral agent to which the patient has had little or no prior exposure. This may involve the use of 1 or more reverse transcriptase inhibitors (RTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs). This study attempts to formally evaluate some of these options in indinavir-experienced patients.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Ritonavir Drug: Nelfinavir mesylate Drug: Levocarnitine Drug: Adefovir dipivoxil Drug: Saquinavir Drug: Delavirdine mesylate	N/A

Detailed Description

Patients are stratified by HIV RNA (2,000 - 20,000 copies/ml versus 20,000 - 200,000 copies/ml), and randomized to 1 of 6 treatment arms as follows:

Arm A: Saquinavir (SQV) plus ritonavir (RTV) plus delavirdine (DLV) plus adefovir dipivoxil placebo.

Arm B: SQV plus RTV plus DLV placebo plus adefovir dipivoxil. Arm C: SQV plus RTV plus DLV plus adefovir dipivoxil. Arm D: SQV plus nelfinavir (NFV) plus DLV plus adefovir dipivoxil placebo. Arm E: SQV plus NFV plus DLV placebo plus adefovir dipivoxil. Arm F: SQV plus NFV plus DLV plus adefovir dipivoxil. In addition to assigned study treatment patients receive an L-carnitine supplement.

Therapy is administered for 24 weeks. Patients who have an average HIV RNA value for Weeks 12 and 16 that is less than 5,000 copies or a least 1 log below their baseline value may continue their assigned study treatment for an additional 24 weeks. [AS PER AMENDMENT 3/30/98: Subjects with plasma HIV RNA greater than 5,000 copies/ml may elect to continue or discontinue study medications in the treatment extension and seek the best available treatment.] [AS PER AMENDMENT 06/11/98: The dose of adefovir dipivoxil is reduced at or after Week 16. Alternatively, patients may discontinue adefovir dipivoxil/placebo and substitute appropriate antiretroviral agent(s) or add appropriate antiretroviral agent(s) to their reduced-dose regimen. Also, at the discretion of the protocol chairperson, patients who have been on study for more than 16 weeks may substitute appropriate FDA-approved antiretroviral agent(s) for any study medication that must be discontinued because of toxicity. Addition of nonnucleoside reverse transcriptase inhibitors, protease inhibitors, or investigational agents is specifically excluded.]

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Activity of the Soft Gelatin Capsule of Saquinavir (SQVsgc) in Combination With Ritonavir or Nelfinavir and Combinations of Delavirdine and/or Adefovir Dipivoxil in HIV-Infected Subjects With Prior Indinavir Use and Viral Loads From 2,000 to 200,000 Copies HIV RNA/ml

Actual Study Completion Date :

Aug 1, 1999

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Concurrent Medication:

Required:

Chemoprophylaxis for Pneumocystis carinii pneumonia for all patients who have a CD4 cell count of equal or less than 200 cells/mm3.

Allowed:

Topical and oral antifungal agents except ketoconazole and itraconazole.
Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic infections.
Antibiotics.
Systemic corticosteroids for 21 days or less for acute problems.
Recombinant erythropoietin (rEPO) and granulocyte-colony stimulating factor (G-CSF, filgrastim).
Regularly prescribed medications such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives (not as a sole form of birth control), megestrol acetate, or testosterone.
Alternative therapies, such as vitamins, acupuncture, and visualization techniques.
[AS PER AMENDMENT 3/30/98: Calcium channel blockers may be used only with caution.]

Patients must have:

HIV-1 infection documented by a licensed ELISA and confirmed by Western blot, HIV culture, HIV antigen, plasma HIV RNA, or a second antibody test other than ELISA.
2,000 to 200,000 HIV-1 RNA copies/ml as measured by any Roche-certified laboratory [AS

PER AMENDMENT 3/30/98:

using the Roche Amplicor HIV-1 Monitor] within 30 days of study entry.
Signed, informed consent from parent or legal guardian for patients less than 18 years of age.

Prior Medication: Required:

More than 6 months cumulative indinavir therapy.
Stable indinavir-containing antiretroviral regimen for at least 4 weeks [2 weeks AS PER AMENDMENT 3/30/98] prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

Any active infection requiring acute treatment within 30 days [21 days AS PER AMENDMENT 3/30/98] prior to study entry.
Unexplained temperature greater than 38.5 degrees for any 7 consecutive days within 30 days prior to study entry.
Malignancy, including Kaposi's sarcoma, that requires systemic chemotherapy.

Concurrent Medication:

Excluded:

Non-protocol-specified immunomodulatory and/or antiretroviral agents.
Systemic cytotoxic chemotherapy.
Ketoconazole, itraconazole, rifampin, rifabutin, alprazolam, amiodarone, astemizole, bepridil, bupropion, cisapride, clorazepate, clozapine, diazepam, encainide, estazolam, flecainide, flurazepam, isotretinoin, meperidine, midazolam, piroxicam, propafenone, propoxyphene, quinidine, terfenadine, triazolam, zolpidem, phenytoin, phenobarbital, carbamazepine, and ergot alkaloids and [ AS PER AMENDMENT 3/30/98: dexamethasone, ergot derivatives, and pimozide].

Avoided:

Herbal medications.

Prior Medication:

Excluded:

At least 2 weeks or more total ritonavir and/or saquinavir (hard gelatin capsule).
NNRTIs (nevirapine, delavirdine, DMP-266, etc.), saquinavir (soft gelatin capsule), nelfinavir, 141W94VX-478, and adefovir dipivoxil.
Immunomodulator [systemic immunomodulator AS PER AMENDMENT 3/30/98] or investigational drug therapy within 30 days prior to entry.
Active immunization within 30 days [21 days AS PER AMENDMENT 3/30/98] prior to entry.

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 Treatment Ctr	San Diego	California	United States	921036325
6	San Francisco Gen Hosp	San Francisco	California	United States	941102859
7	Stanford at Kaiser / Kaiser Permanente Med Ctr	San Francisco	California	United States	94115
8	Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium	San Jose	California	United States	951282699
9	San Mateo AIDS Program / Stanford Univ	Stanford	California	United States	943055107
10	Stanford Univ Med Ctr	Stanford	California	United States	943055107
11	Harbor UCLA Med Ctr	Torrance	California	United States	90502
12	Univ of Colorado Health Sciences Ctr	Denver	Colorado	United States	80262
13	Howard Univ	Washington	District of Columbia	United States	20059
14	Univ of Miami School of Medicine	Miami	Florida	United States	331361013
15	Queens Med Ctr	Honolulu	Hawaii	United States	96816
16	Univ of Hawaii	Honolulu	Hawaii	United States	96816
17	Northwestern Univ Med School	Chicago	Illinois	United States	60611
18	Cook County Hosp	Chicago	Illinois	United States	60612
19	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois	United States	60612
20	Louis A Weiss Memorial Hosp	Chicago	Illinois	United States	60640
21	Indiana Univ Hosp	Indianapolis	Indiana	United States	462025250
22	Methodist Hosp of Indiana / Life Care Clinic	Indianapolis	Indiana	United States	46202
23	State of MD Div of Corrections / Johns Hopkins Univ Hosp	Baltimore	Maryland	United States	212052196
24	Johns Hopkins Hosp	Baltimore	Maryland	United States	21287
25	Boston Med Ctr	Boston	Massachusetts	United States	02118
26	Beth Israel Deaconess - West Campus	Boston	Massachusetts	United States	02215
27	Univ of Minnesota	Minneapolis	Minnesota	United States	55455
28	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York	United States	14215
29	Beth Israel Med Ctr	New York	New York	United States	10003
30	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
31	Chelsea Ctr	New York	New York	United States	10021
32	Cornell Univ Med Ctr	New York	New York	United States	10021
33	St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr	New York	New York	United States	10021
34	Mount Sinai Med Ctr	New York	New York	United States	10029
35	Univ of Rochester Medical Center	Rochester	New York	United States	14642
36	Univ of North Carolina	Chapel Hill	North Carolina	United States	275997215
37	Univ of Cincinnati	Cincinnati	Ohio	United States	452670405
38	Ohio State Univ Hosp Clinic	Columbus	Ohio	United States	432101228
39	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania	United States	19104
40	Univ of Pittsburgh Med Ctr	Pittsburgh	Pennsylvania	United States	15213
41	Brown Univ School of Medicine	Providence	Rhode Island	United States	02908
42	Julio Arroyo	West Columbia	South Carolina	United States	29169
43	Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr	Knoxville	Tennessee	United States	37920
44	Univ of Texas Galveston	Galveston	Texas	United States	775550435
45	Univ of Washington	Seattle	Washington	United States	981224304