A Phase II Randomized Study of the Virologic and Immunologic Effects of d4T vs Zidovudine Plus d4T vs Zidovudine Plus Ddl in HIV-Infected Patients With CD4 Cell Counts Between 300-600/mm3 and Greater Than 12 Weeks Zidovudine Experience

The Effectiveness of Three Drug Combinations in HIV-Infected Patients Who Have Taken Zidovudine for More Than 12 Weeks

Sponsors

Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator: Bristol-Myers Squibb

Source National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

To compare the effect of stavudine (d4T) alone or with zidovudine (AZT) versus didanosine (ddI) alone or with AZT on CD4 counts, HIV RNA levels, and viral load in HIV-infected patients [AS PER AMENDMENT 3/21/97: To compare the effects of d4T alone versus ddI alone versus AZT plus ddI]. To compare the safety of d4T/AZT. AS PER AMENDMENT 3/21/97: To evaluate the pharmacokinetic interactions of AZT and d4T both at an extracellular and intracellular level.

Although AZT and ddI can delay the advancement of HIV disease, the benefit of either of these drugs has proven to be only temporary. d4T, a new nucleoside analog with a favorable toxicity profile and demonstrated activity against HIV, offers an additional therapeutic option. It is reasonably assumed that the benefit of an antiretroviral agent in terms of delaying clinical disease progression is directly related to its ability to achieve and sustain viral suppression; thus, this study measures effects on viral load and CD4 count.

Detailed Description

Although AZT and ddI can delay the advancement of HIV disease, the benefit of either of these drugs has proven to be only temporary. d4T, a new nucleoside analog with a favorable toxicity profile and demonstrated activity against HIV, offers an additional therapeutic option. It is reasonably assumed that the benefit of an antiretroviral agent in terms of delaying clinical disease progression is directly related to its ability to achieve and sustain viral suppression; thus, this study measures effects on viral load and CD4 count.

Patients are randomized in a blinded fashion to receive AZT or placebo in combination with open-label d4T or ddI for up to 48 weeks. AS PER AMENDMENT 3/21/97: The study is now composed of three arms: open-label d4T versus open-label ddI plus blinded AZT placebo versus blinded AZT plus open-label ddI. Patients originally assigned to the d4T + AZT arm, which was closed 10/96, will be given the option of discontinuing AZT and remaining on d4T monotherapy or discontinuing all study drugs. In addition, all study participants will be asked to participate in a pharmacology substudy.

Overall Status Completed
Completion Date November 1997
Phase Phase 2
Study Type Interventional
Enrollment 200
Condition
Intervention

Intervention type: Drug

Intervention name: Stavudine

Intervention type: Drug

Intervention name: Zidovudine

Intervention type: Drug

Intervention name: Didanosine

Eligibility

Criteria:

Inclusion Criteria

Concurrent Medication:

Required for patients whose CD4 count falls below 200 cells/mm3:

- PCP prophylaxis with TMP/SMX, aerosolized pentamidine, or dapsone.

Allowed:

- Atovaquone, IV pentamidine, trimethoprim-dapsone, clindamycin-primaquine, trimetrexate, or TMP/SMX for acute PCP.

- Topical antifungals, clotrimazole, ketoconazole, fluconazole, and amphotericin B for mucosal and esophageal candidiasis.

- Itraconazole.

- Amphotericin B.

- Rifabutin.

- Isoniazid.

- Pyrazinamide.

- Clofazimine.

- Clarithromycin.

- Azithromycin.

- Ethambutol.

- Amikacin.

- Ciprofloxacin.

- Ofloxacin.

- Pyrimethamine.

- Sulfadiazine.

- Clindamycin.

- Ganciclovir.

- G-CSF.

- Acyclovir (up to 1000 mg/day).

- Erythropoietin.

- Antibiotics for bacterial infections.

- Antipyretics.

- Analgesics.

- Antiemetics.

- Rifampin.

Concurrent Treatment:

Allowed:

- Local radiation therapy.

Patients must have:

- HIV infection.

- CD4 count 300-600 cells/mm3.

- More than 12 weeks (was 24 weeks, AMENDED 3/31/96) of total prior AZT ( > 500 mg/day without serious adverse event). Subjects must be actively taking ZDV for at least 4 continuous weeks up to the time of study entry.

- No prior or current history of AIDS.

- No active opportunistic infection.

- Life expectancy of at least 2 years.

- Consent of patient and parent or guardian if less than 18 years of age.

NOTE:

- Protocol is approved for prisoner enrollment.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

- Malignancy requiring systemic cytotoxic chemotherapy.

- Serious underlying medical condition other than HIV that would reduce life expectancy to < 2 years.

Concurrent Medication:

Excluded:

- Antiretrovirals other than study drugs.

- Foscarnet.

Patients with the following prior conditions are excluded:

- Unexplained temperature >= 38.5 C for 7 days or chronic diarrhea (>= three stools daily) for 15 days, if occurring within 30 days prior to study entry.

- History of acute or chronic pancreatitis.

- History of grade 2 or higher peripheral neuropathy.

- History of grade 3 or worse intolerance to 500-600 mg/day AZT.

Prior Medication:

Excluded:

(within 30 days prior to study entry)

- Prior ddI, ddC, 3TC or d4T (more than 2 weeks total).

- Non-nucleoside reverse transcriptase inhibitor or protease inhibitor.

- Biologic response modifiers such as interferon and IL-2.

- Other experimental therapy.

Gender: All

Minimum age: 12 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Location
facility
UCLA CARE Center CRS | Los Angeles, California, 90095, United States
Stanford CRS | Palo Alto, California, 94115, United States
Ucsd, Avrc Crs | San Diego, California, 92103, United States
Ucsf Aids Crs | San Francisco, California, 94110, United States
Harbor-UCLA Med. Ctr. CRS | Torrance, California, 90502, United States
University of Colorado Hospital CRS | Aurora, Colorado, 80262, United States
Children's National Med. Ctr., ACTU | Washington, District of Columbia, 20010, United States
Univ. of Florida Jacksonville NICHD CRS | Jacksonville, Florida, 32209, United States
Univ. of Miami AIDS CRS | Miami, Florida, 33136, United States
Univ. of Hawaii at Manoa, Leahi Hosp. | Honolulu, Hawaii, 96816, United States
Northwestern University CRS | Chicago, Illinois, 60611, United States
Cook County Hosp. CORE Ctr. | Chicago, Illinois, 60612, United States
Rush Univ. Med. Ctr. ACTG CRS | Chicago, Illinois, 60612, United States
Weiss Memorial Hosp. | Chicago, Illinois, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic | Indianapolis, Indiana, 46202, United States
Indiana Univ. School of Medicine, Wishard Memorial | Indianapolis, Indiana, 46202, United States
Methodist Hosp. of Indiana | Indianapolis, Indiana, 46202, United States
Tulane Hemophilia Treatment Ctr. | New Orleans, Louisiana, 70112, United States
Massachusetts General Hospital ACTG CRS | Boston, Massachusetts, 02114, United States
Bmc Actg Crs | Boston, Massachusetts, 02118, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS | Boston, Massachusetts, 02215, United States
Hennepin County Med. Ctr., Div. of Infectious Diseases | Minneapolis, Minnesota, 55415, United States
University of Minnesota, ACTU | Minneapolis, Minnesota, United States
St. Louis ConnectCare, Infectious Diseases Clinic | St Louis, Missouri, 63112, United States
Washington U CRS | St. Louis, Missouri, United States
SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS | Brooklyn, New York, 11203, United States
SUNY - Buffalo, Erie County Medical Ctr. | Buffalo, New York, 14215, United States
Univ. of Rochester ACTG CRS | Rochester, New York, 14642, United States
Univ. of Cincinnati CRS | Cincinnati, Ohio, United States
The Ohio State Univ. AIDS CRS | Columbus, Ohio, 43210, United States
University of Washington AIDS CRS | Seattle, Washington, 98122, United States
San Juan City Hosp. PR NICHD CRS | San Juan, 00936, Puerto Rico
Puerto Rico-AIDS CRS | San Juan, Puerto Rico
Location Countries

Puerto Rico

United States

Verification Date

April 2012

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Study Design Info

Primary purpose: Treatment

Source: ClinicalTrials.gov