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

This study has been completed.
Sponsor:
Collaborators:
Kilimanjaro Christian Medical Centre, Tanzania
Kibongoto National Tuberculosis Hospital, Tanzania
GlaxoSmithKline
Information provided by:
Duke University
ClinicalTrials.gov Identifier:
NCT00851630
First received: February 25, 2009
Last updated: May 2, 2010
Last verified: May 2010

February 25, 2009
May 2, 2010
June 2004
September 2007   (final data collection date for primary outcome measure)
  • Number of Serious Adverse Events (SAEs) [ Time Frame: 104 weeks ] [ Designated as safety issue: Yes ]
    Feasibility and safety of fixed dose combination zidovudine/lamivudine/abacavir in HIV-infected subjects with tuberculosis in a resource-limited setting as assessed by the number of serious adverse events. Serious adverse events included any untoward medical occurrence that resulted in death, was considered life-threatening, required inpatient hospitalization or prolongation of existing hospitalization beyond what was required in the study, or resulted in persistent or resulted in significant disability/incapacity.
  • Tuberculosis-immune Reconstitution Inflammatory Syndrome Events [ Time Frame: 104 weeks ] [ Designated as safety issue: Yes ]
    Tuberculosis-immune reconstitution inflammatory syndrome was defined by the protocol as: a) new persistent fevers (temperature >101.5 degrees Fahrenheit) developing after the initiation of antiretroviral therapy, and not believed to be associated with antiretroviral therapy and without an identifiable source, b) marked worsening or emergence of intrathoracic lymphadenopathy, pulmonary infiltrates or pleural effusions on radiologic examination, or c) worsening or emergence of lymphadenopathy on serial examinations or worsening of other tuberculous lesions.
  • Feasibility and safety of fixed dose combination zidovudine/lamivudine/abacavir in HIV-infected subjects with tuberculosis in a resource-limited setting. [ Time Frame: 104 weeks ] [ Designated as safety issue: Yes ]
  • To assess the impact of delayed versus early initiation strategy for fixed-dose combination zidovudine/lamivudine/abacavir on the rate of tuberculosis-immune reconstitution inflammatory syndromes [ Time Frame: 104 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00851630 on ClinicalTrials.gov Archive Site
  • Plasma HIV Ribonucleic Acid (RNA) Level < 400 Copies/ml [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    The number of subjects with plasma HIV RNA level <400 copies/ml.
  • HIV RNA Level < 50 Copies/ml [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    The number of subjects with plasma HIV RNA level <50 copies/ml.
Not Provided
Not Provided
Not Provided
 
Tuberculosis and Human Immunodeficiency Virus (HIV) Immune Reconstitution Syndrome Trial (THIRST)
A Pilot Study Of Open-Label Fixed Dose Combination Zidovudine/Lamivudine/Abacavir In HIV-Infected Persons With Tuberculosis In Moshi, Tanzania; Tuberculosis And HIV Immune Reconstitution Syndrome Trial (THIRST)

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV
  • Tuberculosis
Drug: 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.
Other Name: Trizivir
  • Experimental: Early
    Initiation of fixed dose combination zidovudine/lamivudine/abacavir 2 weeks after commencing antituberculous therapy
    Intervention: Drug: Fixed dose combination zidovudine/lamivudine/abacavir
  • Experimental: Delayed
    Initiation of fixed dose combination zidovudine/lamivudine/abacavir 8 weeks after commencing antituberculous therapy
    Intervention: Drug: Fixed dose combination zidovudine/lamivudine/abacavir
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
70
September 2007
September 2007   (final data collection date for primary outcome measure)

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.
Both
13 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Tanzania
 
NCT00851630
Pro00013131
Yes
Nathan Thielman, MD, MPH, Duke University Medical Center
Duke University
  • Kilimanjaro Christian Medical Centre, Tanzania
  • Kibongoto National Tuberculosis Hospital, Tanzania
  • GlaxoSmithKline
Principal Investigator: Nathan M Thielman, MD, MPH Duke University
Duke University
May 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP