Tuberculosis and Human Immunodeficiency Virus (HIV) Immune Reconstitution Syndrome Trial (THIRST)

NCT ID: NCT00851630

Last Updated: 2010-05-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-30
• Study Completion Date: 2007-09-30

Brief Summary

The purpose of this study is twofold: (1) to assess the feasibility and safety of fixed dose combination zidovudine/lamivudine/abacavir in HIV infected subjects with tuberculosis in a resource-limited setting, and (2) to assess the impact of delayed versus early initiation strategies for fixed dose combination zidovudine/lamivudine/abacavir on the rate of tuberculosis-associated immune reconstitution inflammatory syndromes.

Conditions

HIV; Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Early

Initiation of fixed dose combination zidovudine/lamivudine/abacavir 2 weeks after commencing antituberculous therapy

Group Type: EXPERIMENTAL

Fixed dose combination zidovudine/lamivudine/abacavir

Intervention Type: DRUG

All subjects will receive fixed dose combination zidovudine(300 mg) / lamivudine (150 mg) / abacavir (300 mg) by mouth twice daily. Medications will be provided as long as deemed beneficial by the site investigator and study subject for up to two years. Toxicity substitutions are allowed per protocol.

Delayed

Initiation of fixed dose combination zidovudine/lamivudine/abacavir 8 weeks after commencing antituberculous therapy

Group Type: EXPERIMENTAL

Fixed dose combination zidovudine/lamivudine/abacavir

Intervention Type: DRUG

All subjects will receive fixed dose combination zidovudine(300 mg) / lamivudine (150 mg) / abacavir (300 mg) by mouth twice daily. Medications will be provided as long as deemed beneficial by the site investigator and study subject for up to two years. Toxicity substitutions are allowed per protocol.

Interventions

Fixed dose combination zidovudine/lamivudine/abacavir

All subjects will receive fixed dose combination zidovudine(300 mg) / lamivudine (150 mg) / abacavir (300 mg) by mouth twice daily. Medications will be provided as long as deemed beneficial by the site investigator and study subject for up to two years. Toxicity substitutions are allowed per protocol.

Intervention Type: DRUG

Other Intervention Names

Trizivir

Eligibility Criteria

Inclusion Criteria

• HIV Infection is documented by rapid HIV test or any licensed enzyme-linked immunosorbent assay (ELISA) test kit and confirmed with a different sample.
• Men or women admitted to Kibongoto or Marangu Hospitals with (a) recent (within 56 days) smear positive tuberculosis (pulmonary or extrapulmonary,) (b)total lymphocyte count <1,200/mm3, and (c) less than 14 days of antituberculous therapy.
• Antiretroviral naive with the exception of regimens used to prevent mother-to-infant transmission of HIV during pregnancy.
• The following laboratory values obtained within 45 days prior to study entry: absolute neutrophil count (ANC) >=700/mm³, hemoglobin > 8 g/dL in women; >9 g/dL in men, serum creatinine <= 1.5 times upper limits of normal, AST <5 times upper limits of normal.
• For all women of reproductive potential (who have not reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation), a negative urine pregnancy test within 48 hours of to study.
• All subjects must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate) and if participating in sexual activity that could lead to pregnancy, the female subject/male partner must use condoms (male or female) without a spermicidal agent.
• Not intending to relocate out of area for the duration of study participation.
• Willingness of subject to adhere to follow up schedule.
• Men and women >= age 13.
• Ability and willingness of subject or legal guardian/representative to give written consent.

Exclusion Criteria

• Serious illness, other than tuberculosis, that requires systematic treatment and/or hospitalization, until either completion of therapy or clinical stability on therapy in the opinion of the investigator for at least 14 days prior to study entry. Oral and vaginal candidiasis, mucocutaneous herpes simples, and other illnesses which are minor in the opinion of the site investigator are exceptions
• Diagnosis of or suspicion of tuberculosis of the central nervous system.
• > 14 days of antituberculous therapy prior to screening.
• > 28 days of antituberculous therapy for active tuberculosis within the 6 months prior to screening.
• Recent past (within 28 days of study entry) or planned use of corticosteroids.
• Any condition that in the opinion of the investigator would compromise the subject's ability to participate in the study.
• Radiation or systemic chemotherapy within 45 days of entry.
• Any immunomodulator, HIV vaccine, or other investigational therapy within 30 days prior to study entry.
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Allergy/sensitivity to any study drugs or their formulations.

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kilimanjaro Christian Medical Centre, Tanzania

OTHER

Sponsor Role: collaborator

Kibongoto National Tuberculosis Hospital, Tanzania

UNKNOWN

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Duke University Medical Center

Principal Investigators

Nathan M Thielman, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Kilimanjaro Christian Medical Centre

Moshi, , Tanzania

Countries

Tanzania

References

Shao HJ, Crump JA, Ramadhani HO, Uiso LO, Ole-Nguyaine S, Moon AM, Kiwera RA, Woods CW, Shao JF, Bartlett JA, Thielman NM. Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania. AIDS Res Hum Retroviruses. 2009 Dec;25(12):1277-85. doi: 10.1089/aid.2009.0100.

Reference Type: RESULT

PMID: 20001518 (View on PubMed)

Other Identifiers

Pro00013131

Identifier Type: -

Identifier Source: org_study_id