Clinical trial NCT00000861: The Addition of Indinavir to Anti-HIV Treatment in HIV-Infected Patients
Official title: A Randomized Trial of Immediate Versus Deferred Indinavir in Addition to Background Antiretroviral Therapy in HIV-Infected Patients With CD4+ Cell Counts Between 200 and 500/mm3 and Plasma HIV RNA Levels >= 10,000 Copies/ml
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Drug Administration Schedule
HIV Protease Inhibitors
CD4 Lymphocyte Count
Indinavir
RNA, Viral
Anti-HIV Agents
Viral Load
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 1900
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effect of immediate versus deferred indinavir (IDV) in addition to background therapy on disease progression or death in patients with CD4+ cell counts between 200 and 500 cells/mm3 and plasma HIV RNA levels \>= 10,000 copies/ml.

This study aims to examine two management strategies, immediate versus deferred IDV therapy, for their clinical effects in the context of background antiretroviral (AR) therapy, given according to current clinical practice. There is an urgent need to identify the optimal use of IDV in patient management, since clinical endpoint studies have not been completed in the United States. Since there is little information about the long term durability of clinical effects, and even less information about the timing of the initiation of protease inhibitor therapy, exploring the disease progression and survival impact of immediate versus delayed use of IDV will yield important information to guide clinical decision making for this group of patients.

Detailed description: This study aims to examine two management strategies, immediate versus deferred IDV therapy, for their clinical effects in the context of background antiretroviral (AR) therapy, given according to current clinical practice. There is an urgent need to identify the optimal use of IDV in patient management, since clinical endpoint studies have not been completed in the United States. Since there is little information about the long term durability of clinical effects, and even less information about the timing of the initiation of protease inhibitor therapy, exploring the disease progression and survival impact of immediate versus delayed use of IDV will yield important information to guide clinical decision making for this group of patients.

Prior to randomization the patient and clinician will determine whether the background therapy will be zidovudine (ZDV) plus lamivudine (3TC) or other background antiretroviral therapy (OBAT). Patients will then be randomized to IDV or matching placebo. AS PER AMENDMENT 06/27/97: The protocol was closed as of 03/25/97, and all patients have been unblinded to their assigned treatment. Patients still on study medication are eligible for the protocol extension. Patients who were randomized to immediate IDV may continue on therapy for up to an additional 4 months. All study therapy, both for those on immediate or delayed therapy, must be discontinued on 10/24/97.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Topical and/or antifungal agents, except ketoconazole.
* Treatment, maintenance, or chemoprophylaxis with approved agents for OIs will be given as clinically indicated.
* Clinically indicated antibiotics, unless excluded.
* Systemic corticosteroid use for \<21 days for acute problems is permitted as clinically indicated. However, chronic systemic corticosteroid use should be avoided.
* Recombinant erythropoietin (rEPO) and granulocyte-colony stimulating factor (G-CSF, filgrastim).
* Didanosine (ddI).
* Regularly prescribed medications, such as antipyretics, antidepressants, oral contraceptives, megestrol acetate, testosterone, or any other medication.

Patients must have:

* A working diagnosis of HIV infection.
* A CD4+ count between 200 and 500 cells/mm3.
* Signed, informed parental consent if patient is less than 18.

NOTE:

* The DAIDS Clinical Science Research Committee (CSRC) has deemed this protocol appropriate for prisoner enrollment.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following conditions or symptoms are excluded:

Febrile illness with temperature \> 38.5 degrees C (101.3 degrees F) within 3 days prior to study entry.

Concurrent Medication:

Excluded:

* Non-nucleoside reverse transcriptase inhibitors.
* Protease inhibitors except IDV.
* Rifabutin and rifampin.
* Ketoconazole.
* Terfenadine, astemizole, cisapride, triazolam and midazolam.

Patients with any of the following prior conditions are excluded:

* History of prior saquinavir (SQV) therapy for more than 14 days.
* History of any prior protease inhibitor therapy other than SQV.
* History of serious opportunistic infection.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Community Consortium of San Francisco
state: California
city: Denver
country: United States
facility: Denver CPCRA / Denver Public Hlth
state: Colorado
city: Washington
country: United States
facility: Veterans Administration Med Ctr / Regional AIDS Program
state: District of Columbia
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Chicago
country: United States
facility: AIDS Research Alliance - Chicago
state: Illinois
city: New Orleans
country: United States
facility: Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
state: Louisiana
city: Detroit
country: United States
facility: Comprehensive AIDS Alliance of Detroit
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hosp
state: Michigan
city: Camden
country: United States
facility: Southern New Jersey AIDS Cln Trials / Dept of Med
state: New Jersey
city: Newark
country: United States
facility: North Jersey Community Research Initiative
state: New Jersey
city: New York
country: United States
facility: Harlem AIDS Treatment Group / Harlem Hosp Ctr
state: New York
city: Portland
country: United States
facility: Portland Veterans Adm Med Ctr / Rsch & Education Grp
state: Oregon
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Richmond
country: United States
facility: Richmond AIDS Consortium
state: Virginia
Study officials:
name: Saravolatz L
role: STUDY_CHAIR
name: Crane L
role: STUDY_CHAIR
name: Mayers D
role: STUDY_CHAIR
References:
citation: Spector SA, Barker C, Buhles W, Feinberg J, Montague P, Weingeist T, DeArmond B. A randomized, controlled study of immediate vs deferred ganciclovir therapy in AIDS patients with cytomegalovirus peripheral retinitis. Int Conf AIDS. 1991 Jun 16-21;7(1):44 (abstract no MB86)