A Prospective, Randomized, Open-Label, Comparative Trial of Dideoxyinosine (ddI) Versus Dideoxycytidine (ddC) in HIV-Infected Patients Who Are Intolerant of or Who Have Failed Zidovudine (AZT) Therapy

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Hoffmann-La Roche
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000969
First received: November 2, 1999
Last updated: September 28, 2013
Last verified: September 2013
  Purpose

To evaluate and compare the effectiveness and toxicity associated with didanosine ( ddI ) and zalcitabine ( dideoxycytidine; ddC ) in patients with HIV infection who are intolerant of or have failed zidovudine ( AZT ) therapy.

Alternative and less toxic treatments need to be investigated for the treatment of HIV infection. Studies have shown that the dideoxynucleosides ddI and ddC may be effective antiretroviral agents in the treatment of HIV-infected individuals. However, ddI and ddC have yet to be compared on the basis of patient survival, drug tolerance, immunologic and virologic effectiveness, and the incidence of opportunistic infection or opportunistic malignancy. Results of this study will yield information regarding the relative therapeutic benefits and toxicities of each drug while providing alternative treatment to patients who are unable to tolerate or have had progression of disease while on AZT.


Condition Intervention
HIV Infections
Drug: Zalcitabine
Drug: Didanosine

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Open-Label, Comparative Trial of Dideoxyinosine (ddI) Versus Dideoxycytidine (ddC) in HIV-Infected Patients Who Are Intolerant of or Who Have Failed Zidovudine (AZT) Therapy

Resource links provided by NLM:


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

Estimated Enrollment: 400
Study Completion Date: September 1992
Detailed Description:

Alternative and less toxic treatments need to be investigated for the treatment of HIV infection. Studies have shown that the dideoxynucleosides ddI and ddC may be effective antiretroviral agents in the treatment of HIV-infected individuals. However, ddI and ddC have yet to be compared on the basis of patient survival, drug tolerance, immunologic and virologic effectiveness, and the incidence of opportunistic infection or opportunistic malignancy. Results of this study will yield information regarding the relative therapeutic benefits and toxicities of each drug while providing alternative treatment to patients who are unable to tolerate or have had progression of disease while on AZT.

After baseline screening, patients are randomized to one of two treatment arms (ddI or ddC). Subjects are evaluated biweekly for the first 4 weeks of study, at 2 months, and every other month thereafter. Three dose levels of ddI (based on patient's weight at study entry) are compared with two dose levels of ddC (also based on patient weight). Patients who reach a new progression-of-disease primary endpoint after at least 12 weeks of treatment or a drug intolerance endpoint have the option of switching over to the alternate study drug; however, participants are encouraged to remain on their original drug assignment whenever possible. For any switchover, patients must be off the originally assigned drug for at least 72 hours before switching. Only one switchover is allowed.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Acyclovir (if patient is also receiving ddC, clinical monitoring should be more frequent).
  • Analgesics, antiemetics, antidiarrheal agents, or other necessary treatment for symptomatic therapy.
  • Interferons for maintenance therapy of Kaposi's sarcoma.
  • GM-CSF.

Required:

  • Prophylaxis against Pneumocystis carinii pneumonia (PCP) if their absolute CD4+ lymphocyte count is < 200 cells/mm3 at study entry. PCP prophylaxis for patient with CD4+ counts between 200 and 300 cells/mm3 is at discretion of patient's primary physician.
  • NOTE: There is potential interaction of ddI and dapsone.

Concurrent Treatment:

Allowed:

  • Transfusion, erythropoietin.

Patients must have the following:

  • Zidovudine (AZT) failure after having received a cumulative duration of at least 6 months.
  • AZT intolerance - rechallenge is not required for patients exhibiting = or > grade III cutaneous symptoms.
  • Diagnosis of AIDS or CD4+ = or < 300 cells/mm3 OR AIDS-defining illness other than Kaposi's sarcoma.
  • Willingness and ability to comply with protocol.
  • Informed consent must be obtained for all study participants in accordance with state law, local IRB requirements, and 45 CFR Part 46. AMENDED 11/19/90 to include assent by minors if they are physically able, in addition to consent by parents.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Any disorders for which the study drugs are contraindicated (didanosine (ddI)) is contraindicated in renal impairment, heart disease, receiving renal dialysis.
  • Active opportunistic infection.

Concurrent Medication:

Excluded:

  • Other antiretroviral agents.
  • Use of drugs associated with peripheral neuropathy or use of agents that may cause pancreatitis including intravenous pentamidine and alcohol should be restricted or avoided.

Concurrent Treatment:

Excluded:

  • Other concurrent antiretroviral clinical trials.

Patients with the following are excluded:

  • History of pancreatitis, peripheral neuropathy, uncontrolled seizures, renal impairment, heart disease, stage 2 or higher ADC.
  • Any other disorders for which the study drugs are contraindicated, i.e., ddI is contraindicated in renal impairment, patients receiving renal dialysis, and heart disease.
  • Receiving acute therapy for active AIDS defining opportunistic infection on enrollment.

Prior Medication:

Excluded:

  • Didanosine (ddI).
  • Dideoxycytidine (ddC) .

Excessive alcohol use that, in investigator's opinion, puts patient at risk of developing pancreatic disease.

  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: NCT00000969

Locations
United States, California
Community Consortium of San Francisco
San Francisco, California, United States, 94110
United States, Colorado
Denver CPCRA / Denver Public Hlth
Denver, Colorado, United States, 802044507
United States, Connecticut
Hill Health Corp
New Haven, Connecticut, United States, 06519
United States, Delaware
Wilmington Hosp / Med Ctr of Delaware
Wilmington, Delaware, United States, 19899
United States, District of Columbia
Veterans Administration Med Ctr / Regional AIDS Program
Washington, District of Columbia, United States, 20422
United States, Georgia
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30308
United States, Illinois
AIDS Research Alliance - Chicago
Chicago, Illinois, United States, 60657
United States, Louisiana
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
New Orleans, Louisiana, United States, 70112
United States, Michigan
Henry Ford Hosp
Detroit, Michigan, United States, 48202
Comprehensive AIDS Alliance of Detroit
Detroit, Michigan, United States, 48201
United States, New Jersey
North Jersey Community Research Initiative
Newark, New Jersey, United States, 071032842
United States, New York
Bronx Lebanon Hosp Ctr
Bronx, New York, United States, 10456
Harlem AIDS Treatment Group / Harlem Hosp Ctr
New York, New York, United States, 10037
Clinical Directors Network of Region II
New York, New York, United States, 10011
United States, Oregon
Portland Veterans Adm Med Ctr / Rsch & Education Grp
Portland, Oregon, United States, 972109951
United States, Virginia
Richmond AIDS Consortium
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Bristol-Myers Squibb
Hoffmann-La Roche
Investigators
Study Chair: Kaplan C
Study Chair: Crane L
Study Chair: Abrams D
  More Information

Additional Information:
Publications:
Hogan CH, Hodges JS, Mugglin A, Peterson PM, Abrams DI, Saravolatz L. The perils of visit-driven endpoints in antiretroviral trials. Int Conf AIDS. 1996 Jul 7-12;11(1):237 (abstract no TuB522)
Abrams D, Goldman A, Launer C, Korvick J, Crane L, Deyton L. Results of a randomized open-label comparison trial of ddI and ddC in HIV infected patients who are intolerant of or have failed ZDV therapy; CPCRA 002. The Terry Beirn Community Programs for Clinical Research on AIDS. Int Conf AIDS. 1993 Jun 6-11;9(1):67 (abstract no WS-B24-4)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000969     History of Changes
Other Study ID Numbers: CPCRA 002, 11554
Study First Received: November 2, 1999
Last Updated: September 28, 2013
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Zalcitabine
Didanosine
Drug Evaluation
Zidovudine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
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
Zalcitabine
Didanosine
Zidovudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 28, 2014