A Study of Dideoxyinosine (ddI) in HIV-Infected Children Who Have Not Had Success With Zidovudine or Who Cannot Take Zidovudine

HIV Infections Clinical Trial

Official title:

A Randomized Comparative Trial of Two Doses of 2',3'-Dideoxyinosine (ddI) in Children With Symptomatic HIV Infection Who Are Either Unresponsive to Zidovudine and/or Who Are Intolerant to Zidovudine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000963
• Other study ID #: ACTG 144
• Secondary ID: 11119
• Status: Completed
• Phase: Phase 2
• Est. completion date: September 1995

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the effectiveness, safety, and tolerance of two doses of didanosine (ddI) in the treatment of children with symptomatic HIV disease who have had to discontinue zidovudine (AZT) because of intolerance and/or who have experienced progressive disease while on AZT.

The progression of immunodeficiency due to HIV infection can be delayed by using AZT. The benefits of AZT in adults with AIDS and severe AIDS-related complex (ARC) appear to last for approximately 12 to 18 months, at which time most patients have progressive deterioration. Recently published literature has described a reduced sensitivity of HIV isolated from patients after prolonged AZT treatment. Although the clinical significance of this is unclear, it makes the development of new antiretroviral drugs important.

Description:

The progression of immunodeficiency due to HIV infection can be delayed by using AZT. The benefits of AZT in adults with AIDS and severe AIDS-related complex (ARC) appear to last for approximately 12 to 18 months, at which time most patients have progressive deterioration. Recently published literature has described a reduced sensitivity of HIV isolated from patients after prolonged AZT treatment. Although the clinical significance of this is unclear, it makes the development of new antiretroviral drugs important.

Children who show AZT intolerance and/or progressive disease after 6 months of AZT therapy receive oral ddI at 1 of 2 doses for a minimum of 48 weeks, with a 48-week extension. Patients are seen for clinical and laboratory evaluations at scheduled times during the study. (Per 5/12/92 amendment, new patients will not be enrolled in the pharmacokinetics studies.) Per 10/31/94 amendment: Patients are eligible to receive blinded study drug for an additional 8-16 weeks after the final on-study visit, but no later than 2/15/95.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: September 1995
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 18 Years

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Prophylaxis treatment for Pneumocystis carinii pneumonia (PCP).

• Immunoglobulin.

• Maintenance therapy with amphotericin B (l mg/kg) up to 5 days/week.

Concurrent Treatment:

Allowed:

• Blood transfusions.

Prior Medication:

Allowed:

• Prophylaxis treatment for Pneumocystis carinii pneumonia (PCP).

Patients enrolled in ACTG 128 and ACTG 138 must meet study end points or meet protocol definitions for being permanently off zidovudine (AZT) before enrolling in this study.

• Patients currently enrolled in ACTG 051 who have not reached the study end points but who meet the entry criteria for ACTG 144 may be co-enrolled in ACTG 144.

• Patient or guardian available to give written informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded.

• Hypersensitivity to didanosine (ddI).

• Symptomatic cardiomyopathy.

• Seizures that are not well controlled by ongoing anticonvulsant therapy.

• Symptomatic pancreatitis.

• Grade 1 or higher peripheral neuropathy.

• Active malignancy requiring chemotherapy.

Concurrent Medication:

Excluded:

• Zidovudine (AZT), other antiretroviral agents, biological modifiers, and investigational medications.

Avoid:

• Drugs with potential to cause peripheral neuropathy or pancreatitis.

Patients with the following are excluded:

• Active malignancy requiring concomitant chemotherapy.

Prior Medication:

Excluded:

• Antiretroviral agents other than zidovudine (AZT) or dideoxycytidine (ddC) within 4 weeks of study entry.

• Immunomodulating agents such as interferons, isoprinosine, or interleukin-2 within 2 weeks of entry.

• Any other experimental therapy within 1 week of entry.

• Drugs that have or will cause prolonged neutropenia, significant pancreatitis, significant nephrotoxicity, or peripheral neuropathy within 1 week of entry.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infections

Intervention

Drug:
• Didanosine

Locations

Country	Name	City	State
Puerto Rico	Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.	Bayamon
Puerto Rico	San Juan City Hosp. PR NICHD CRS	San Juan
Puerto Rico	Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS	San Juan
United States	Children's Hospital at Albany Medical Center, Dept. of Peds.	Albany	New York
United States	Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases	Atlanta	Georgia
United States	Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases	Baltimore	Maryland
United States	Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology	Baltimore	Maryland
United States	BMC, Div. of Ped Infectious Diseases	Boston	Massachusetts
United States	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts
United States	Bronx-Lebanon Hosp. IMPAACT CRS	Bronx	New York
United States	SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS	Brooklyn	New York
United States	Med. Univ. of South Carolina, Div. of Ped. Infectious Diseases	Charleston	South Carolina
United States	Chicago Children's CRS	Chicago	Illinois
United States	Cook County Hosp.	Chicago	Illinois
United States	Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease	Chicago	Illinois
United States	Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.	Chicago	Illinois
United States	Case CRS	Cleveland	Ohio
United States	Children's Med. Ctr. Dallas	Dallas	Texas
United States	Children's Hospital of Michigan NICHD CRS	Detroit	Michigan
United States	DUMC Ped. CRS	Durham	North Carolina
United States	Univ. of Connecticut Health Ctr., Dept. of Ped.	Farmington	Connecticut
United States	North Shore-Long Island Jewish Health System, Dept. of Peds.	Great Neck	New York
United States	Texas Children's Hosp. CRS	Houston	Texas
United States	Long Beach Memorial Med. Ctr., Miller Children's Hosp.	Long Beach	California
United States	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California
United States	Usc La Nichd Crs	Los Angeles	California
United States	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida
United States	UMDNJ - Robert Wood Johnson	New Brunswick	New Jersey
United States	Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease	New Haven	Connecticut
United States	Schneider Children's Hosp., Div. of Infectious Diseases	New Hyde Park	New York
United States	Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU	New Orleans	Louisiana
United States	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana
United States	Columbia IMPAACT CRS	New York	New York
United States	Harlem Hosp. Ctr. NY NICHD CRS	New York	New York
United States	Incarnation Children's Ctr.	New York	New York
United States	Metropolitan Hosp. NICHD CRS	New York	New York
United States	NYU Med. Ctr., Dept. of Medicine	New York	New York
United States	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California
United States	St. Joseph's Hosp. & Med. Ctr. of New Jersey	Paterson	New Jersey
United States	St. Christopher's Hosp. for Children	Philadelphia	Pennsylvania
United States	The Children's Hosp. of Philadelphia IMPAACT CRS	Philadelphia	Pennsylvania
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California
United States	UCSF Pediatric AIDS CRS	San Francisco	California
United States	UW School of Medicine - CHRMC	Seattle	Washington
United States	Baystate Health, Baystate Med. Ctr.	Springfield	Massachusetts
United States	SUNY Stony Brook NICHD CRS	Stony Brook	New York
United States	SUNY Upstate Med. Univ., Dept. of Peds.	Syracuse	New York
United States	Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases	Torrance	California
United States	Children's National Med. Ctr., ACTU	Washington	District of Columbia
United States	Howard Univ. Washington DC NICHD CRS	Washington	District of Columbia
United States	WNE Maternal Pediatric Adolescent AIDS CRS	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (2)

Carey VJ, Yong F, Frenkel L, McKinney R. Enhancing the prognostic value of bodily growth histories in HIV-positive pediatric cohorts. Int Conf AIDS. 1996 Jul 7-12;11(2):134 (abstract no WeC3444)

Perrier M, Schwarz T, Gonzalez O, Brounts S. Squamous cell carcinoma invading the right temporomandibular joint in a Belgian mare. Can Vet J. 2010 Aug;51(8):885-7. — View Citation