Clinical trial NCT00002035: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Didanosine
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2001-08-31
Enrollment: 300
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Univ of Arizona / Health Science Ctr
state: Arizona
city: New Haven
country: United States
facility: Yale Univ Med School
state: Connecticut
city: Fort Lauderdale
country: United States
facility: G E Morey Jr
state: Florida
city: Orlando
country: United States
facility: VP Med Services / HHCS Research Institute Inc
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Hines
country: United States
facility: Edward Hines Veterans Administration Hosp
state: Illinois
city: Wichita
country: United States
facility: Univ of Kansas School of Medicine
state: Kansas
city: Detroit
country: United States
facility: Harper Hosp
state: Michigan
city: Albany
country: United States
facility: Albany Med College / AIDS Treatment Ctr
state: New York
city: Toledo
country: United States
facility: Med College of Ohio
state: Ohio
city: Philadelphia
country: United States
facility: Univ of Pennsylvania / HIV Clinic
state: Pennsylvania
city: Dallas
country: United States
facility: Univ of Texas Southwestern Med Ctr of Dallas
state: Texas
city: Galveston
country: United States
facility: Univ TX Galveston Med Branch
state: Texas
city: San Antonio
country: United States
facility: Audie L Murphy Veterans Administration Hosp
state: Texas
city: Salt Lake City
country: United States
facility: Univ of Utah School of Medicine
state: Utah
city: Hampton
country: United States
facility: Dr Stephen L Green
state: Virginia
city: Milwaukee
country: United States
facility: Milwaukee County Med Complex
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: UPR School of Medicine
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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)