Double-Blind Comparison of the Efficacy of Continued Zidovudine Versus 2',3'-Dideoxyinosine (ddI) (BMY-40900) for the Treatment of Patients With AIDS or AIDS-Related Complex and Increasing Symptomatology Despite Treatment With Zidovudine

HIV Infections Clinical Trial

Official title:

Double-Blind Comparison of the Efficacy of Continued Zidovudine Versus 2',3'-Dideoxyinosine (ddI) (BMY-40900) for the Treatment of Patients With AIDS or AIDS-Related Complex and Increasing Symptomatology Despite Treatment With Zidovudine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002035
• Other study ID #: 039B
• Secondary ID: AI454-010
• Status: Completed
• Phase: N/A
• First received: November 2, 1999
• Last updated: August 4, 2011
• Est. completion date: April 1992

Study information

• Verified date: August 2011
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To compare the efficacy and safety of orally administered didanosine (ddI) with orally administered zidovudine (AZT) in the treatment of patients who exhibit increasing clinical deterioration despite treatment with AZT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: April 1992
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed for Hematologic toxicity:

• Erythropoietin.

• Colony-Stimulating Factors.

• Allowed for prophylaxis of Pneumocystis carinii pneumonia (PCP):

• Aerosolized pentamidine.

• Trimethoprim/sulfamethoxazole.

• Dapsone.

• NOTE:

• If intravenous pentamidine is required for treatment of PCP, study drug should be suspended until one week after completion of intravenous pentamidine.

• Allowed:

• Prophylactic or suppressive therapy begun prior to study entry with the exception of neurotoxic agents (as defined in the protocol).

Concurrent Treatment:

Allowed:

• Transfusions for hematologic toxicity.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Active acute AIDS defining infection.

• Clinical evidence of acute pancreatitis in the last two years or chronic pancreatitis.

• Dementia of such severity that patient cannot give informed consent.

• Grade 2 or worse peripheral neuropathy as defined by Targeted Neuropathy Score (Schaumberg).

• Prior Cytomegalovirus disease requiring ongoing systemic ganciclovir therapy.

• Extensive Kaposi's sarcoma or other malignancy requiring systemic cytotoxic myelosuppressive or neurotoxic chemotherapy.

• Cardiomyopathy or the need for antiarrhythmic therapy.

• Inability to tolerate at least 600 mg per day of zidovudine (AZT).

• Seizures within the last 6 months or the need for anticonvulsant therapy.

Concurrent Medication:

Excluded:

• Ganciclovir (DHPG).

• Myelosuppressive or neurotoxic chemotherapy.

• Antiarrhythmic therapy.

• Anticonvulsant therapy.

• Neurotoxic agents (as defined in the protocol).

• NOTE:

• If intravenous pentamidine is required for treatment of Pneumocystis carinii pneumonia (PCP), study drug should be suspended until 1 week after completion of intravenous pentamidine.

Patients with the following are excluded:

• Symptoms and conditions defined in the Patient Exclusion Co-Existing Conditions field.

• Average of two sequential CD4 counts from SciCor Clinical Laboratories in the 30 days prior to study entry > 300 cells/mm3.

Prior Medication:

Excluded, participation in studies using:

• Dideoxyinosine (ddI).

• 2',3'-Dideoxy-2',3'-didehydrothymidine (d4T).

• Dideoxycytidine (ddC).

• Excluded within one month of study entry:

• Any other experimental antiretroviral compounds.

Patients must:

• Have documented HIV positivity via ELISA.

• Meet CDC criteria for AIDS or AIDS related complex (ARC).

• Have received zidovudine (AZT) for = or > 6 months and tolerated a dose of at least 500 mg per day without significant hematologic toxicity.

• Have no acute AIDS defining opportunistic infection, but may be receiving suppressive therapy for such infections.

• Demonstrate at least one of the following criteria for clinical deterioration despite AZT therapy within 4 weeks prior to study entry (8 weeks prior for weight loss):

• involuntary weight loss of more than 5 percent of the body weight occurring over the 8 week period prior to study entry, Karnofsky score = or > 50 but demonstrating a fall = or > 20 from previous level of functioning (assessment must be persistent on two occasions at least 14 days apart), unexplained fever of = or > 38 degrees C (despite evaluation defined in protocol) for more than 7 days, appearance of newly diagnosed oral hairy leukoplakia or oral candidiasis, or recurrence of a previously quiescent multidermatomal varicella-zoster, appearance of dermatologic afflictions (e.g. psoriasis, molluscum contagiosum, or newly diagnosed seborrheic dermatitis), appearance of chronic herpetic ulcers not responsive to acyclovir therapy.

Required:

• Zidovudine (AZT) for = or > 6 months prior to study entry.

Study Design

Endpoint Classification: Safety Study, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• AIDS-Related Complex
• HIV Infections

Intervention

Drug:
• Zidovudine

• Didanosine

Locations

Country	Name	City	State
Puerto Rico	UPR School of Medicine	San Juan
United States	Albany Med College / AIDS Treatment Ctr	Albany	New York
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Univ of Texas Southwestern Med Ctr of Dallas	Dallas	Texas
United States	Harper Hosp	Detroit	Michigan
United States	G E Morey Jr	Fort Lauderdale	Florida
United States	Univ TX Galveston Med Branch	Galveston	Texas
United States	Dr Stephen L Green	Hampton	Virginia
United States	Edward Hines Veterans Administration Hosp	Hines	Illinois
United States	Milwaukee County Med Complex	Milwaukee	Wisconsin
United States	Yale Univ Med School	New Haven	Connecticut
United States	VP Med Services / HHCS Research Institute Inc	Orlando	Florida
United States	Univ of Pennsylvania / HIV Clinic	Philadelphia	Pennsylvania
United States	Univ of Utah School of Medicine	Salt Lake City	Utah
United States	Audie L Murphy Veterans Administration Hosp	San Antonio	Texas
United States	Med College of Ohio	Toledo	Ohio
United States	Univ of Arizona / Health Science Ctr	Tucson	Arizona
United States	Univ of Kansas School of Medicine	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

Ruedy N, et al. Results of long term follow-up of a double blind study of ddI vs continued AZT among individuals with CD4s 200-500/mm3. Int Conf AIDS. 1994 Aug 7-12;10(2):16 (abstract no 358B)

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm