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
  Purpose

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.


Condition Intervention Phase
HIV
Tuberculosis
Drug: Fixed dose combination zidovudine/lamivudine/abacavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 70
Study Start Date: June 2004
Study Completion Date: September 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Early
Initiation of fixed dose combination zidovudine/lamivudine/abacavir 2 weeks after commencing antituberculous therapy
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: Delayed
Initiation of fixed dose combination zidovudine/lamivudine/abacavir 8 weeks after commencing antituberculous therapy
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

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00851630

Locations
Tanzania
Kilimanjaro Christian Medical Centre
Moshi, Tanzania
Sponsors and Collaborators
Duke University
Kilimanjaro Christian Medical Centre, Tanzania
Kibongoto National Tuberculosis Hospital, Tanzania
GlaxoSmithKline
Investigators
Principal Investigator: Nathan M Thielman, MD, MPH Duke University
  More Information

Publications:
Responsible Party: Nathan Thielman, MD, MPH, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00851630     History of Changes
Other Study ID Numbers: Pro00013131
Study First Received: February 25, 2009
Results First Received: March 15, 2009
Last Updated: May 2, 2010
Health Authority: United States: Institutional Review Board
Tanzania: National Institute for Medical Research
Tanzania: Food & Drug Administration

Keywords provided by Duke University:
HIV
Tuberculosis
Treatment Naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Tuberculosis
Immune Reconstitution Inflammatory Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Zidovudine
Lamivudine
Abacavir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 09, 2014