A Trial of Two Doses of 2',3'-Dideoxycytidine (ddC) in the Treatment of Children With Symptomatic HIV Infection Who Are Intolerant of AZT and/or Who Show Progressive Disease While on AZT

NCT ID: NCT00000653

Last Updated: 2021-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1995-06-30

Brief Summary

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To evaluate and compare the long-term (48-177 weeks) safety, tolerance, and efficacy of two doses of zalcitabine ( dideoxycytidine; ddC ) taken orally every 8 hours in children with symptomatic HIV infection who have one of the following: intolerance to zidovudine ( AZT ) (development of toxicity during prolonged AZT therapy), demonstrated disease progression after 6 months of AZT therapy, OR both AZT intolerance and disease progression after 6 months of AZT therapy.

As useful as AZT appears to be in the treatment of patients infected with HIV, it is associated with significant toxicity in some patients, and it does not prevent ultimate progression to AIDS and eventual mortality. Thus, there is a clear need for new antiretroviral drugs, and ddC is one such promising agent.

Detailed Description

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As useful as AZT appears to be in the treatment of patients infected with HIV, it is associated with significant toxicity in some patients, and it does not prevent ultimate progression to AIDS and eventual mortality. Thus, there is a clear need for new antiretroviral drugs, and ddC is one such promising agent.

Patients receive oral ddC for 48 to 177 weeks.

Conditions

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HIV Infections

Keywords

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Zalcitabine Drug Evaluation Acquired Immunodeficiency Syndrome AIDS-Related Complex

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Zalcitabine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Concurrent Medication:

Allowed:

* Procrit.
* Amphotericin B (1 mg/kg up to 5 days/week).
* Prophylaxis treatment as per ACTG recommendations for Pneumocystis carinii pneumonia.
* Acyclovir (up to 1000 mg/day PO; for \> 1000 mg/day PO or for any IV dose, suggest interrupting ddC).
* Ketoconazole (up to 10 mg/kg/day).
* Nystatin.
* Aspirin, acetaminophen, sedatives, and barbiturates (for up to 72 hours).
* Isoniazid (INH), if there is no evidence of peripheral neuropathy at entry. Children should receive pyridoxine, 25
* 50 mg/day to avoid possible INH-associated neuropathy.
* Trimethoprim / sulfamethoxazole (T/S).
* Immunoglobulin therapy.
* Aerosolized pentamidine.
* Drugs with little nephro-, hepato-, cytotoxicity that the patient has been taking and tolerating well for an ongoing condition.

Concurrent Treatment:

Allowed:

* Immunoglobulin therapy.
* Nutritional support (for children with wasting syndrome and/or malnutritional) including hyperalimentation (TPN) of dietary supplements.

AMENDED:

* Patients enrolled in ACTG 051 may participate in ACTG 138 if they show intolerance to AZT or show disease progression after 6 months of AZT therapy and meet entry criteria for the study.

ORIGINAL design:

* Patients enrolled in ACTG protocols 051 or 128 must meet study end points or meet protocol definitions for being permanently off zidovudine (AZT) before enrolling in this protocol.

Patients must have the following:

* Absence of acute opportunistic infection at time of entry.
* However, if patient is successfully treated for opportunistic infection and has remained stable for 2 weeks after treatment, the patient is then allowed to enter the study. Children receiving maintenance therapy for \> 4 weeks are eligible.
* Parent or guardian available to give written informed consent.

Allowed at time of study entry:

* Prophylaxis treatment as per ACTG recommendations, for Pneumocystis carinii pneumonia (PCP).
* Immunoglobulin therapy.

Prior Medication:

AMENDED:

* AZT or ddI up until study entry, other antiretrovirals up until 4 weeks of study entry

Allowed:

* Zidovudine (AZT) within 4 weeks of entry.
* Dideoxyinosine (ddI) within 43 weeks of entry if no peripheral neuropathy has been observed while receiving ddI.
* Other toxicities observed while on ddI must resolve to level 2 or better before patient can begin treatment with ddC.
* Vitamin, folate, iron supplements.

Exclusion Criteria

Co-existing Condition:

AMENDED:

* 04-25-91 Additional excluded symptoms and conditions:
* Symptomatic cardiomyopathy.
* Seizures which are not well controlled by ongoing anticonvulsant therapy.
* Active malignancy requiring concomitant chemotherapy.
* Symptomatic pancreatitis.
* Grade I or greater peripheral neuropathy.
* Receiving concomitant zidovudine (AZT).
* Patients with the following conditions or symptoms are excluded:
* Acute bacterial infections requiring IV or oral antibiotic treatment at time of entry.
* Known hypersensitivity to dideoxycytidine (ddC).

Concurrent Medication:

Excluded:

* Other antiviral agents, biological modifiers, and investigational medications.
* Drugs with potential to cause peripheral neuropathy, including chloramphenicol, iodoquinol, phenytoin, ethionamide, gold, ribavirin, vincristine, cisplatin, dapsone, disulfiram, glutethimide, hydralazine, metronidazole, nitrofurantoin.

Patients with the following are excluded:

* Acute bacterial infections requiring IV or oral antibiotic treatment at time of entry.
* Known hypersensitivity to dideoxycytidine (ddC).
* Active opportunistic infection requiring treatment with an excluded concomitant medication.

Prior Medication:

Excluded:

* Antiretroviral agents (other than zidovudine (AZT) or didanosine (ddI)) within 4 weeks of entry.
* Immunomodulating agents such as interferons, isoprinosine, or interleukin-2 within 2 weeks of entry.
* Any other experimental therapy, drugs that cause prolonged neutropenia, significant nephrotoxicity, or peripheral neuropathy within 1 week of entry.
Minimum Eligible Age

3 Months

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Spector SA

Role: STUDY_CHAIR

Locations

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UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS

Los Angeles, California, United States

Site Status

Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.

Oakland, California, United States

Site Status

UCSD Maternal, Child, and Adolescent HIV CRS

San Diego, California, United States

Site Status

UCSF Pediatric AIDS CRS

San Francisco, California, United States

Site Status

Children's National Med. Ctr., ACTU

Washington D.C., District of Columbia, United States

Site Status

Univ. of Miami Ped. Perinatal HIV/AIDS CRS

Miami, Florida, United States

Site Status

Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases

Atlanta, Georgia, United States

Site Status

Cook County Hosp.

Chicago, Illinois, United States

Site Status

Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.

Chicago, Illinois, United States

Site Status

Chicago Children's CRS

Chicago, Illinois, United States

Site Status

Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU

New Orleans, Louisiana, United States

Site Status

Tulane/LSU Maternal/Child CRS

New Orleans, Louisiana, United States

Site Status

Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases

Baltimore, Maryland, United States

Site Status

HMS - Children's Hosp. Boston, Div. of Infectious Diseases

Boston, Massachusetts, United States

Site Status

BMC, Div. of Ped Infectious Diseases

Boston, Massachusetts, United States

Site Status

Baystate Health, Baystate Med. Ctr.

Springfield, Massachusetts, United States

Site Status

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, United States

Site Status

UMDNJ - Robert Wood Johnson

New Brunswick, New Jersey, United States

Site Status

SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS

Brooklyn, New York, United States

Site Status

North Shore-Long Island Jewish Health System, Dept. of Peds.

Great Neck, New York, United States

Site Status

Schneider Children's Hosp., Div. of Infectious Diseases

New Hyde Park, New York, United States

Site Status

NYU Med. Ctr., Dept. of Medicine

New York, New York, United States

Site Status

Metropolitan Hosp. NICHD CRS

New York, New York, United States

Site Status

Columbia IMPAACT CRS

New York, New York, United States

Site Status

Harlem Hosp. Ctr. NY NICHD CRS

New York, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Bronx-Lebanon Hosp. IMPAACT CRS

The Bronx, New York, United States

Site Status

UNC at Chapel Hill School of Medicine - Dept. of Peds., Div. of Immunology & Infectious Diseases

Chapel Hill, North Carolina, United States

Site Status

DUMC Ped. CRS

Durham, North Carolina, United States

Site Status

St. Christopher's Hosp. for Children

Philadelphia, Pennsylvania, United States

Site Status

Texas Children's Hosp. CRS

Houston, Texas, United States

Site Status

Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.

Bayamón, , Puerto Rico

Site Status

Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS

San Juan, , Puerto Rico

Site Status

San Juan City Hosp. PR NICHD CRS

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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.

Reference Type BACKGROUND
PMID: 21037891 (View on PubMed)

Spector SA, Blanchard S, Connor EM, Salgo MP, McNamara J. Results of a clinical trial comparing two doses of 2'3'-dideoxycytidine (ddC) in the treatment of children with symptomatic human immunodeficiency virus (HIV) infection who were intolerant or had failed zidovudine (ZDV) therapy (ACTG 138). The Pediatric AIDS Clinical Trials Group. American Pediatric Society 104th annual meeting and Society for Pediatric Research 63rd annual meeting; 1994 May 2-5; Seattle. Pediatr AIDS HIV Infect. 1994 Oct;5(5):323 (unnumbered abstract)

Reference Type BACKGROUND

Other Identifiers

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11113

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 138

Identifier Type: -

Identifier Source: org_study_id