A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children

HIV Infections Clinical Trial

Official title:

A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000637
• Other study ID #: ACTG 152
• Secondary ID: 11127
• Status: Completed
• Phase: Phase 3
• Est. completion date: September 1996

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 compare the effectiveness of treatment with zidovudine (AZT) compared to didanosine (ddI) and compared to the combination of AZT and ddI as determined by survival and disease progression. To compare the relative safety and tolerance of AZT versus ddI versus AZT plus ddI in symptomatic HIV infected children; to compare the virological and immunological parameters in the three treatment groups. AZT has been shown to delay the progression of AIDS in HIV infected individuals. However, bone marrow toxicity is a frequent adverse effect. Also, HIV resistance to AZT sometimes occurs in patients who initially respond to treatment, but later have progression of the disease. Thus, new drug treatments are needed. Studies of ddI in adults and children indicate some effectiveness of the drug. A direct comparison of AZT and ddI treatment in children has not been made. Combination antiviral treatment (AZT plus ddI) may give added therapeutic benefit to children.

Description:

AZT has been shown to delay the progression of AIDS in HIV infected individuals. However, bone marrow toxicity is a frequent adverse effect. Also, HIV resistance to AZT sometimes occurs in patients who initially respond to treatment, but later have progression of the disease. Thus, new drug treatments are needed. Studies of ddI in adults and children indicate some effectiveness of the drug. A direct comparison of AZT and ddI treatment in children has not been made. Combination antiviral treatment (AZT plus ddI) may give added therapeutic benefit to children.

Patients are placed by random selection into one of three groups to receive either AZT alone, ddI alone, or AZT and ddI. This is a double-blind study: neither patient nor treating physician knows which group patient is in. If patients are receiving either AZT or ddI alone and they develop drug toxicity (after dose reduction), or if HIV disease progresses, the alternative single drug is offered. If patients receiving both drugs develop drug toxicity (despite dose reduction) or if HIV disease progresses, they discontinue study drug and are offered the best alternative therapy. PER AMENDMENT 6/26/95: Initial monotherapy AZT arm is unblinded and no further crossover therapy for any arm is permitted. Patients who reach crossover criteria on initial blinded ddI or AZT+ddI will be unblinded and permanently discontinued from study drugs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 819
• Est. completion date: September 1996
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 17 Years

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Acetaminophen, ibuprofen, or aspirin, but not on a continual basis for > 72 hours.

• Systemic ketoconazole and fluconazole for acute therapy.

Recommended:

• Prophylaxis for PCP. (Primary prophylaxis with TMP / SMX is encouraged.) IV pentamidine may be used in selected cases if not administered on a weekly basis.

Patients must have the following:

• HIV infection.

• Children randomized prior to their eighteenth birthday are eligible. Co-enrollment in either ACTG 179 or 189 is permitted.

Prior Medication:

Allowed:

• Up to six weeks of antiretroviral or immunomodulator treatment excluding steroids and intravenous immunoglobulin.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Active malignancy.

• Pancreatitis or history of pancreatitis within one year prior to study entry associated with compatible symptoms.

• History of uncontrolled seizure disorder.

• Grade 3 or higher peripheral neuropathy.

• Cardiomyopathy.

Concurrent Medication:

Excluded:

• Chemotherapy for malignancy.

• Oral acidifying agents.

• Acetaminophen, ibuprofen, or aspirin on a continual basis for > 72 hours.

• Ketoconazole or fluconazole for prophylaxis.

• Drugs with potential to cause peripheral neuropathy or pancreatitis should not be given daily for > 4 weeks.

Patients with the following are excluded:

• Active malignancy.

• Pancreatitis or history of pancreatitis within one year prior to study entry associated with compatible symptoms.

• History of uncontrolled seizure disorder.

• Grade 3 or higher peripheral neuropathy.

Prior Medication:

Excluded:

• Steroids.

• Intravenous immunoglobulin.

• Antiretroviral drugs or specific immunomodulator treatment (excluding steroids and intravenous immunoglobulin) for > 6 weeks and within 7 days prior to study entry.

Prior Treatment:

Excluded:

• Red blood cell transfusion within four weeks prior to study entry.

Ongoing drug or alcohol use.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Zidovudine

• Didanosine

Locations

Country	Name	City	State
Puerto Rico	Ramon Ruiz Arnau Univ Hosp / Pediatrics	Bayamon
Puerto Rico	San Juan City Hosp	San Juan
Puerto Rico	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan
Puerto Rico	UPR Children's Hosp / UPR School of Medicine	San Juan
United States	Children's Hosp at Albany Med Ctr	Albany	New York
United States	Emory Univ Hosp / Pediatrics	Atlanta	Georgia
United States	Johns Hopkins Hosp - Pediatric	Baltimore	Maryland
United States	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland
United States	Univ of Alabama at Birmingham Schl of Med / Pediatrics	Birmingham	Alabama
United States	Boston City Hosp / Pediatrics	Boston	Massachusetts
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Bronx Lebanon Hosp Ctr / Pediatrics	Bronx	New York
United States	Lincoln Hosp Ctr	Bronx	New York
United States	King's County Hosp Ctr / Pediatrics	Brooklyn	New York
United States	SUNY - Brooklyn	Brooklyn	New York
United States	SUNY / Health Sciences Ctr at Brooklyn / Pediatrics	Brooklyn	New York
United States	Children's Hosp Pact Prog / Children's Hosp of Buffalo	Buffalo	New York
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Cook County Hosp	Chicago	Illinois
United States	Univ of Chicago Children's Hosp	Chicago	Illinois
United States	Univ of Illinois College of Medicine / Pediatrics	Chicago	Illinois
United States	Cincinnati Children's Hosp / Univ Hosp	Cincinnati	Ohio
United States	Case Western Reserve Univ	Cleveland	Ohio
United States	Columbus Children's Hosp	Columbus	Ohio
United States	Children's Med Ctr of Dallas	Dallas	Texas
United States	Children's Hosp of Denver	Denver	Colorado
United States	Children's Hosp of Michigan	Detroit	Michigan
United States	Kaiser Permanente / UCLA Med Ctr	Downey	California
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	Univ of Connecticut Health Ctr	Farmington	Connecticut
United States	North Shore Univ Hosp	Great Neck	New York
United States	Hermann Hosp / Univ Texas Health Science Ctr	Houston	Texas
United States	Texas Children's Hosp / Baylor Univ	Houston	Texas
United States	UCSD Med Ctr / Pediatrics / Clinical Sciences	La Jolla	California
United States	Long Beach Memorial (Pediatric)	Long Beach	California
United States	Cedars Sinai / UCLA Med Ctr	Los Angeles	California
United States	Harbor - UCLA Med Ctr / UCLA School of Medicine	Los Angeles	California
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	UCLA Med Ctr / Pediatric	Los Angeles	California
United States	Saint Jude Children's Research Hosp of Memphis	Memphis	Tennessee
United States	Univ of Miami (Pediatric)	Miami	Florida
United States	Robert Wood Johnson Med School / Hershey Med Ctr	New Brunswick	New Jersey
United States	UMDNJ - Robert Wood Johnson Med School / Pediatrics	New Brunswick	New Jersey
United States	Yale Univ Med School	New Haven	Connecticut
United States	Schneider Children's Hosp	New Hyde Park	New York
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr / Pediatrics	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Cornell Univ Med College	New York	New York
United States	Harlem Hosp Ctr	New York	New York
United States	Incarnation Children's Ctr / Columbia Presbyterian Med Ctr	New York	New York
United States	Metropolitan Hosp Ctr	New York	New York
United States	Mount Sinai Med Ctr / Pediatrics	New York	New York
United States	Saint Luke's - Roosevelt Hosp Ctr	New York	New York
United States	Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	Children's Hosp of Oakland	Oakland	California
United States	Huntington Memorial Hosp / Children's Hosp of Los Angeles	Pasadena	California
United States	Children's Hosp of Philadelphia	Philadelphia	Pennsylvania
United States	Saint Christopher's Hosp for Children	Philadelphia	Pennsylvania
United States	Hemophilia Ctr of Western PA / Univ of Pittsburgh	Pittsburgh	Pennsylvania
United States	Rhode Island Hosp / Brown Univ	Providence	Rhode Island
United States	Univ of Rochester Medical Center	Rochester	New York
United States	St Louis Univ School of Medicine	Saint Louis	Missouri
United States	Univ of California / San Diego Treatment Ctr	San Diego	California
United States	UCSF / Moffitt Hosp - Pediatric	San Francisco	California
United States	Children's Hosp of Seattle	Seattle	Washington
United States	Baystate Med Ctr of Springfield	Springfield	Massachusetts
United States	Stanford Univ School of Medicine / Pediatrics	Stanford	California
United States	State Univ of New York at Stony Brook	Stony Brook	New York
United States	SUNY Health Sciences Ctr at Syracuse / Pediatrics	Syracuse	New York
United States	Westchester Hosp	Valhalla	New York
United States	Children's Hosp of Washington DC	Washington	District of Columbia
United States	Georgetown Univ Med Ctr	Washington	District of Columbia
United States	Howard Univ Hosp	Washington	District of Columbia
United States	Univ of Massachusetts Med Ctr	Worcester	Massachusetts

Sponsors (3)

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

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (12)

Capparelli EV, Englund JA, Connor JD, Spector SA, McKinney RE, Palumbo P, Baker CJ. Population pharmacokinetics and pharmacodynamics of zidovudine in HIV-infected infants and children. J Clin Pharmacol. 2003 Feb;43(2):133-40. — View Citation

Chantry CJ, Byrd RS, Englund JA, Baker CJ, McKinney RE Jr; Pediatric AIDS Clinical Trials Group Protocol 152 Study Team. Growth, survival and viral load in symptomatic childhood human immunodeficiency virus infection. Pediatr Infect Dis J. 2003 Dec;22(12):1033-9. — View Citation

Englund JA, Baker CJ, McKinney RE, Raskino CL, Fowler MG, Lifschitz MC. Results of ACTG 152, a randomized comparative trial of zidovudine (ZDV), didanosine (ddI), and ZDV/ddI combination therapy in symptomatic HIV-infected children. Program Abstr Intersci Conf Antimicrob Agents Chemother. 1996 Sep 15-18:213 (abstract no I150)

Englund JA, Baker CJ, Raskino C, McKinney RE, Petrie B, Fowler MG, Pearson D, Gershon A, McSherry GD, Abrams EJ, Schliozberg J, Sullivan JL. Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children. AIDS Clinical Trials Group (ACTG) Study 152 Team. N Engl J Med. 1997 Jun 12;336(24):1704-12. — View Citation

Glick ME. CTG studies yield results. AIDS Clinical Trials Group. NIAID AIDS Agenda. 1995 Spring:8-9. — View Citation

Grubman S. Pediatric treatment update. GMHC Treat Issues. 1996 Mar;10(3):7-9. — View Citation

James JS. AZT, ddI, and ddC combinations at FDA advisory hearing. Food and Drug Administration. AIDS Treat News. 1996 Apr 5;(no 244):6. — View Citation

McKinney RE Jr, Wilfert C. Growth as a prognostic indicator in children with human immunodeficiency virus infection treated with zidovudine. AIDS Clinical Trials Group Protocol 043 Study Group. J Pediatr. 1994 Nov;125(5 Pt 1):728-33. — View Citation

Nielsen K, Wei LS, Sim MS, Deveikis A, Keller M, Stiehm ER, Frenkel LM, Bryson YJ. Correlation of clinical progression in human immunodeficiency virus-infected children with in vitro zidovudine resistance measured by a direct quantitative peripheral blood lymphocyte assay. J Infect Dis. 1995 Aug;172(2):359-64. — View Citation

Palumbo PE, Raskino C, Fiscus S, Pahwa S, Fowler MG, Spector SA, Englund JA, Baker CJ. Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-infected infants and children. JAMA. 1998 Mar 11;279(10):756-61. — View Citation

Raskino C, Pearson DA, Baker CJ, Lifschitz MH, O'Donnell K, Mintz M, Nozyce M, Brouwers P, McKinney RE, Jimenez E, Englund JA. Neurologic, neurocognitive, and brain growth outcomes in human immunodeficiency virus-infected children receiving different nucleoside antiretroviral regimens. Pediatric AIDS Clinical Trials Group 152 Study Team. Pediatrics. 1999 Sep;104(3):e32. — View Citation

Rogers MF, Mofenson LM, Moseley RR. Reducing the risk of perinatal HIV transmission through zidovudine therapy: treatment recommendations and implications. J Am Med Womens Assoc (1972). 1995 May-Aug;50(3-4):78-82, 93. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references