A Study of Zidovudine in HIV-Infected Patients Who Have Hemophilia

NCT ID: NCT00001104

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 538 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1990-02-28

Brief Summary

Study A: To determine whether treatment with zidovudine (ZDV) will delay or change the disease process in hemophilic patients who have HIV infection with no symptoms. The major clinical question is whether patients who receive chronic ZDV therapy will have a delay in the development of AIDS or AIDS-related complex (ARC). The pharmacokinetics (blood levels) of ZDV in hemophilic patients will also be studied.

Study B: To determine if ZDV therapy changes the risk of a hemophiliac transmitting HIV to his wife or other female sexual partner. To determine the effectiveness of counseling and education on the behaviors of the wives that place them at risk for HIV infection. To determine if antibodies to HIV either appear or disappear from the blood of any of the wives during the study.

Study A: Individuals who are infected with HIV can benefit from therapy with an effective anti-AIDS virus agent. ZDV is a potent inhibitor of HIV in vitro (test tube) and is safe in humans at the dose planned. It may be effective in preventing the development of AIDS or ARC in hemophiliacs who have the HIV antibody in their blood. The pharmacokinetic studies are especially important because the high prevalence of hepatic disease in this population may affect the metabolism and blood levels of ZDV.

Study B: HIV is transmitted by sexual contact, and wives of infected hemophilic patients have become infected during long-term sexual relationships. Transmission of the virus does not occur during casual family contact. This study will aid in determining if therapy influences the transmission of HIV, because the wives of hemophiliacs generally have no risk for HIV infection other than sexual contact with their spouse.

Detailed Description

Study A: Individuals who are infected with HIV can benefit from therapy with an effective anti-AIDS virus agent. ZDV is a potent inhibitor of HIV in vitro (test tube) and is safe in humans at the dose planned. It may be effective in preventing the development of AIDS or ARC in hemophiliacs who have the HIV antibody in their blood. The pharmacokinetic studies are especially important because the high prevalence of hepatic disease in this population may affect the metabolism and blood levels of ZDV.

Study B: HIV is transmitted by sexual contact, and wives of infected hemophilic patients have become infected during long-term sexual relationships. Transmission of the virus does not occur during casual family contact. This study will aid in determining if therapy influences the transmission of HIV, because the wives of hemophiliacs generally have no risk for HIV infection other than sexual contact with their spouse.

Study A: Patients selected for the study are randomly assigned to placebo (inactive medication) or ZDV taken every 4 hours while the patient is awake for a total of 5 doses per day. The patient's immune function and clinical condition are monitored with periodic virus cultures, p24 antigen assays, estimates of lymphocyte type and numbers, cell surface markers, and frequent clinical evaluations to see if these are markers of drug efficacy. Patients continue on their regimen until the final analysis of the data, which could occur up to 3 years after the last patient is entered into the study. Amendment: Based on data from ACTG 019 this protocol has been closed to further accrual. All patients entered in this study will be unblinded as to treatment received. Patients will be informed of results of ACTG 019 and be requested to sign a modified statement of consent approved by the local Institutional Review Board. All patients currently receiving study therapy will be offered open-label ZDV. Patients temporarily discontinued from study therapy at this time will be offered open-label ZDV when toxicity resolves (less than or equal to Grade 2 hemoglobin or neutrophil toxicity, less than or equal to Grade 1 all other toxicities). Patients who have been permanently discontinued from study therapy will not be eligible for open-label ZDV through this protocol. Modification of dose is recommended, however, patients who elect to continue current dose of ZDV after being informed of results of ACTG 019 will be allowed to do so. All patients enrolled in this study will continue to be followed until termination of this study. Above amendment added 11/01/89.

Study B: The wife or other female sexual partner is interviewed once at the beginning of the study and again when Study A is completed. The interview takes about 10 minutes and includes questions about the couple's sexual activity to help define the risk of becoming infected with HIV. In addition, blood is drawn to test for antibodies to HIV. The questionnaire and blood sample will be repeated at the time the patient is switched from blinded study therapy to open-label ZDV. (AMENDED 11/01/89) The results of the blood test are given to the person being tested. Information about the transmission of HIV and counseling are provided. It is recommended that the wife abstain from sexual contact with her husband, but if she does not, the use of condoms or condoms plus a spermicide is recommended. The decision about the type of precautions to take does not influence the opportunity to participate in the study.

Conditions

HIV Infections

Keywords

Sex Behavior; T-Lymphocytes; HIV Antibodies; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Zidovudine; Hemophilia A

Study Design

• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT

Interventions

Zidovudine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Concurrent Medication:

Allowed with caution for Study A:

• Hepatotoxic drugs.

Patients in Study A must have:

• Hemophilia with no symptoms for AIDS. Most patients will have well-established factor 8 or 9 deficiency. However, patients with other coagulation diseases, such as factor 5 deficiency, and von Willebrand disease, will also be acceptable for the study.

Wives in Study B are included even if they are known to be seropositive or are not sexually active at the time the study starts.

Prior Medication:

Allowed for Study A:

• Patients who were on the Phase I ZDV study, ACTG 017, or are on ACTG 062 may enter after waiting 3 weeks.

Exclusion Criteria

Co-existing Condition:

Patients in Study A with the following symptoms or conditions are excluded:

• AIDS-defining illness.
• Severe ARC.
• Severe or prolonged toxicity.

Concurrent Medication:

Excluded for Study A:

• Isoniazid or rifampin.
• Treatment for Pneumocystis carinii pneumonia (PCP), oral candidiasis, and localized cutaneous herpes simplex or zoster infections.
• Probenecid.
• Aspirin on a regular basis, or for more than 72 hours without contacting the investigator.
• Drugs causing neutropenia or significant risk of nephrotoxicity.

Patients in Study A with the following prior conditions are excluded:

• AIDS-defining opportunistic infection or malignancy.
• Unexplained temperature greater than 38 C for more than 5 consecutive days or more than 10 days in any 30-day period in the 2 years prior to entry.
• Unexplained diarrhea defined as three or more liquid stools per day, persisting more than 7 days within 2 years prior to entry.
• Unintentional weight loss of greater than 10 lbs. or more than 10 percent of usual body weight within 2 years prior to study entry.
• Oral hairy leukoplakia at any time prior to entry.
• Oral candidiasis unrelated to the use of antibiotic therapy for more than 2 weeks within 2 years prior to entry or within the past 3 months.
• Herpes zoster within 2 years prior to entry into the study.

Prior Medication:

Excluded for Study A:

• Antiretroviral agents, including ZDV, ribavirin, HPA-23, rifampin, AL721 within 8 weeks of study entry.
• Significant course of immunomodulating agents such as steroids (greater than 1 week), isoprinosine, thymic factors within 3 months of study entry.
• Any other experimental therapy within 3 months of study entry.

Discouraged but not forbidden for Study B:

• Sexual contact with infected husband.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas C. Merigan

Role: STUDY_CHAIR

Locations

Los Angeles County - USC Med Ctr

Los Angeles, California, United States

Univ of California / San Diego Treatment Ctr

San Diego, California, United States

Stanford Univ School of Medicine

Stanford, California, United States

Northwestern Univ Med School

Chicago, Illinois, United States

Cook County Hosp

Chicago, Illinois, United States

Chicago Children's Memorial Hosp

Chicago, Illinois, United States

Indiana Univ Hosp

Indianapolis, Indiana, United States

Tulane Univ School of Medicine

New Orleans, Louisiana, United States

Children's Hosp of Boston

Boston, Massachusetts, United States

Univ of Massachusetts Med Ctr

Worcester, Massachusetts, United States

Univ of Minnesota

Minneapolis, Minnesota, United States

Cornell Univ Med Ctr

New York, New York, United States

Mount Sinai Med Ctr

New York, New York, United States

Univ of Rochester Medical Center

Rochester, New York, United States

Univ of North Carolina

Chapel Hill, North Carolina, 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

Ohio State Univ Hosp Clinic

Columbus, Ohio, United States

Milton S Hershey Med Ctr

Hershey, Pennsylvania, United States

Hemophilia Ctr of Western PA / Univ of Pittsburgh

Pittsburgh, Pennsylvania, United States

Univ of Pittsburgh Med School

Pittsburgh, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

Univ of Washington

Seattle, Washington, United States

Countries

United States

References

Price W, Merigan T, Peterman T. Condom usage reported by female sexual partners of asymptomatic HIV seropositive hemophilic men. Int Conf AIDS. 1989 Jun 4-9;5:420 (abstract no ThBP30)

Reference Type: BACKGROUND

Other Identifiers

11012

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 036

Identifier Type: -

Identifier Source: org_study_id