Safety and Efficacy of Zidovudine for Asymptomatic HIV-Infected Individuals

HIV Infections Clinical Trial

Official title:

Safety and Efficacy of Zidovudine for Asymptomatic HIV-Infected Individuals

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000736
• Other study ID #: ACTG 019
• Secondary ID: 10995
• Status: Completed
• Phase: Phase 3
• Est. completion date: February 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 determine if treatment with zidovudine (AZT) will delay or prevent the onset of AIDS or AIDS related complex (ARC) in individuals infected with HIV but who do not have symptoms of AIDS or ARC. Also, to compare the dose of AZT found to be useful in AIDS and severe ARC with a lower dose to see if side effects can be reduced.

Results from several studies show that a high percentage of people infected with HIV will eventually develop AIDS or ARC unless an effective treatment is found. Because AZT is known to prolong survival in patients with AIDS or severe ARC and has acceptable toxicity in advanced disease, it is reasonable to try it in less advanced cases.

Description:

Results from several studies show that a high percentage of people infected with HIV will eventually develop AIDS or ARC unless an effective treatment is found. Because AZT is known to prolong survival in patients with AIDS or severe ARC and has acceptable toxicity in advanced disease, it is reasonable to try it in less advanced cases.

Patients entered in the study are randomly assigned to one of two doses of AZT or to placebo (inactive medication). Patients take 3 capsules 5 times a day (every 4 hours from 8 am until 12 pm).

The capsules contain either AZT or placebo and are identical in appearance so that neither patient nor physician knows which treatment the patient is receiving. The higher dose corresponds to the dose found to be useful in patients with AIDS or severe ARC. Patients visit the clinic every 2 weeks for the first 16 weeks, then once a month after that for evaluation. Treatment will continue until the results from the study have been analyzed, which could be as long as 3 years. If side effects occur, the dose of study medication will be decreased or temporarily stopped. If the side effects are severe, then study medication will be stopped permanently.

AMENDED: Effective with Version 4 (900226), dosing for ALL patients on Phase 2 study drug, regardless of CD4+ substudy, will proceed as open-label AZT. Original treatment assignments employed in the > 500 cells/mm3 substudy during the period from August 16, 1989 through the release of this new version. Also, toxicity management and dose modification of AZT for patients receiving Phase 2 study drug have been changed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3200
• Est. completion date: February 1995
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

Patients must:

• Be HIV seropositive and asymptomatic.

• Have normal neurologic exam as defined by the Micro Neuro-AIDS assessment.

Concurrent Medication

• Required: Prophylaxis for Pneumocystis carinii pneumonia (PCP). Aerosolized pentamidine is preferred but if not possible, Trimethoprim / sulfamethoxazole 1 DS tablet per day or Dapsone 50 - 100 mg per day is allowed.

Exclusion Criteria

• Active drug or alcohol abuse sufficient to prevent adequate compliance with study therapy in the investigator's opinion.

Co-existing Condition:

Patients with the following diseases or conditions are excluded:

• Hemophilia.

• Oral candida infection documented by morphology or by response to antifungal therapy within 2 years of study entry.

• Oral hairy leukoplakia at any time prior to study entry.

• Herpes zoster infection (including single dermatome infection) within 2 years of study entry.

• Active diarrhea as defined by 3 or more liquid stools per day.

• Temperature > 37.8 degrees C.

• Grade 1 impairment on two or more items (mild AIDS dementia complex) in the ACTG Micro Neuro-AIDS Assessment.

• Prior history of malignancy other than cutaneous basal cell carcinomas or cervical carcinoma in situ.

Patients with the following are excluded from entry:

• AIDS or AIDS-related complex defining symptoms.

• Significant, chronic underlying medical illnesses which would impair continuous participation in this 3-year clinical trial.

• Hemophilia.

Prior Medication: Excluded:

• Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP).

• Other experimental medications.

• Excluded within 60 days of study entry:

• Antiretroviral drugs or immunomodulators (biologic response modifiers).

• Excluded within 120 days of study entry:

• Systemic corticosteroids.

Prior Treatment: Excluded within 3 months of study entry:

• Blood transfusion.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Zidovudine

Locations

Country	Name	City	State
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	Beth Israel Deaconess - West Campus	Boston	Massachusetts
United States	Beth Israel Deaconess Med Ctr	Boston	Massachusetts
United States	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts
United States	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York
United States	Bronx Veterans Administration / Mount Sinai Hosp	Bronx	New York
United States	Jack Weiler Hosp / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Med Ctr / Bronx Municipal Hosp	Bronx	New York
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois
United States	Holmes Hosp / Univ of Cincinnati Med Ctr	Cincinnati	Ohio
United States	Univ Hosp of Cleveland / Case Western Reserve Univ	Cleveland	Ohio
United States	Columbus Children's Hosp	Columbus	Ohio
United States	Ohio State Univ Hosp Clinic	Columbus	Ohio
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	City Hosp Ctr at Elmhurst / Mount Sinai Hosp	Elmhurst	New York
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	UCLA CARE Ctr	Los Angeles	California
United States	Univ of Minnesota	Minneapolis	Minnesota
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr / Peter Krueger Clinic	New York	New York
United States	Cornell Univ Med Ctr	New York	New York
United States	Mem Sloan - Kettering Cancer Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Saint Luke's - Roosevelt Hosp Ctr	New York	New York
United States	Summitt Med Ctr / San Francisco Gen Hosp	Oakland	California
United States	Palo Alto Veterans Adm Med Ctr / Stanford Univ	Palo Alto	California
United States	Univ of Pittsburgh Med School	Pittsburgh	Pennsylvania
United States	Univ of Rochester Medical Center	Rochester	New York
United States	St Louis Regional Hosp / St Louis Regional Med Ctr	Saint Louis	Missouri
United States	Univ of California / San Diego Treatment Ctr	San Diego	California
United States	Children's Hosp of San Francisco	San Francisco	California
United States	San Francisco AIDS Clinic	San Francisco	California
United States	San Francisco AIDS Clinic / San Francisco Gen Hosp	San Francisco	California
United States	Stanford at Kaiser / Kaiser Permanente Med Ctr	San Francisco	California
United States	Univ of Washington	Seattle	Washington
United States	Stanford Univ School of Medicine	Stanford	California
United States	SUNY - Stony Brook	Stony Brook	New York
United States	SUNY / State Univ of New York	Syracuse	New York
United States	Harbor UCLA Med Ctr	Torrance	California
United States	George Washington Univ Med Ctr	Washington	District of Columbia
United States	Julio Arroyo	West Columbia	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (9)

Choi S, Lagakos SW, Schooley RT, Volberding PA. CD4+ lymphocytes are an incomplete surrogate marker for clinical progression in persons with asymptomatic HIV infection taking zidovudine. Ann Intern Med. 1993 May 1;118(9):674-80. — View Citation

Jacobson MA, Gundacker H, Hughes M, Fischl M, Volberding P. Zidovudine side effects as reported by black, Hispanic, and white/non-Hispanic patients with early HIV disease: combined analysis of two multicenter placebo-controlled trials. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jan 1;11(1):45-52. — View Citation

Lenderking WR, Gelber RD, Cotton DJ, Cole BF, Goldhirsch A, Volberding PA, Testa MA. Evaluation of the quality of life associated with zidovudine treatment in asymptomatic human immunodeficiency virus infection. The AIDS Clinical Trials Group. N Engl J Med. 1994 Mar 17;330(11):738-43. — View Citation

Vella S, Giuliano M, Dally LG, Agresti MG, Tomino C, Floridia M, Chiesi A, Fragola V, Moroni M, Piazza M, et al. Long-term follow-up of zidovudine therapy in asymptomatic HIV infection: results of a multicenter cohort study. The Italian Zidovudine Evaluation Group. J Acquir Immune Defic Syndr (1988). 1994 Jan;7(1):31-8. — View Citation

Volberding P. The value of the CD4+ count of 500 cells/microliters. Drugs. 1995;49 Suppl 1:4-8; discussion 38-40. Review. — View Citation

Volberding PA, Lagakos SW, Grimes JM, Stein DS, Balfour HH Jr, Reichman RC, Bartlett JA, Hirsch MS, Phair JP, Mitsuyasu RT, et al. The duration of zidovudine benefit in persons with asymptomatic HIV infection. Prolonged evaluation of protocol 019 of the AIDS Clinical Trials Group. JAMA. 1994 Aug 10;272(6):437-42. — View Citation

Volberding PA, Lagakos SW, Grimes JM, Stein DS, Rooney J, Meng TC, Fischl MA, Collier AC, Phair JP, Hirsch MS, et al. A comparison of immediate with deferred zidovudine therapy for asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per cubic millimeter. AIDS Clinical Trials Group. N Engl J Med. 1995 Aug 17;333(7):401-7. — View Citation

Volberding PA, Lagakos SW, Koch MA, Pettinelli C, Myers MW, Booth DK, Balfour HH Jr, Reichman RC, Bartlett JA, Hirsch MS, et al. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. N Engl J Med. 1990 Apr 5;322(14):941-9. — View Citation

Wu AW, Rubin HR, Mathews WC, Ware JE Jr, Brysk LT, Hardy WD, Bozzette SA, Spector SA, Richman DD. A health status questionnaire using 30 items from the Medical Outcomes Study. Preliminary validation in persons with early HIV infection. Med Care. 1991 Aug;29(8):786-98. — View Citation