An evaluation of the impact of early initiation of Highly Active Anti-Retroviral Therapy (HAART) on Tuberculosis (TB) treatment outcomes for TB patients co-infected with Human Immunodeficiency Virus (HIV)

ISRCTN ISRCTN77861053
DOI https://doi.org/10.1186/ISRCTN77861053
Secondary identifying numbers South Africa (A50560), Zambia (A50636), Uganda (A30224) and Tanzania (A30213)
Submission date
29/03/2006
Registration date
29/03/2006
Last edited
30/09/2014
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Philip Onyebujoh
Scientific

World Health Organization
20 Avenue Appia
Geneva-27
CH-1211
Switzerland

Phone +41 (0)22 791 4478
Email onyebujohp@who.int

Study information

Study designRandomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Scientific title
Study acronymTB-HAART
Study objectivesThat early concomitant treatment with TB and HIV medications may improve TB outcomes and improve survival.

As of 12/07/2011 the anticipated end date for this trial has been updated from 30/05/2009 to 30/06/2014.
Ethics approval(s)Ethics approval received on the 17/08/2005.
Health condition(s) or problem(s) studiedTuberculosis (TB) and Human Immunodeficiency Virus (HIV) co-infections
InterventionPlacebo controlled trial.

Patients with TB-HIV co-infection with CD4 counts above 220, to be randomised into combined treatment with anti-TB and HIV medications and then HAART after six months, or anti-TB plus placebo for six months and then HAART thereafter.

All patients will be on HAART after six months, and post-trial medication is provided by the governments of participating countries.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Highly Active Anti-Retroviral Therapy (HAART)
Primary outcome measureThe proportion of subjects reaching the composite endpoint of treatment failure or death at six months after the initiation of short-course chemotherapy for TB.
Secondary outcome measures1. The proportion of patients with TB relapse in the 24 months after initiation of short course chemotherapy in the two treatment groups
2. The proportion of patients reaching the multiple endpoint of treatment failure, relapse or death evaluated at 24 months after TB treatment initiation
3. The safety and tolerability of HAART used concomitantly with anti-TB medication
Overall study start date30/05/2006
Completion date30/06/2014

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants1900
Key inclusion criteria1. Aged 18 to 65 years
2. HIV treatment naive patients (established by history)
3. CD 4 T-cell count between 220-500 cells/l
4. No history of previous anti-TB chemotherapy
5. A traceable home address and contact details to facilitate home visits with a firm commitment to remain traceable and to be able to access a defined treatment/service point for 24 months
6. Not enrolled in any other drug or treatment trials
7. Informed consent for HIV testing (since the study population will be smear positive TB patients co-infected with HIV)
8. Informed consent to participate in the trial
9. For female subjects, the following conditions are to be met:
9.1. Has been post-menopausal for at least one year, or
9.2. Is surgically incapable of bearing children, or
9.3. Is of childbearing potential and all of the following conditions are met:
9.3.1. Had a normal menstrual flow within one month before study entry
9.3.2. Has a negative pregnancy test (urine) immediately before study entry (and later confirmed by serum pregnancy test)
9.3.3. Must agree to use an accepted method of contraception (i.e. barrier methods or intrauterine device [IUD]). The subject must agree to continue with the same method throughout the study
Note: If a patient is using a long-acting hormonal contraceptive (such as Depot-Provera), the patient can be enrolled in the study, however she should be advised to use it in conjunction with a barrier method or IUD due to the known pharmacokinetic interaction between the various study medications and hormonal contraceptives. If an oral hormonal agent is in use, the patient should be advised to change the method of contraception in favour of barrier methods.
Key exclusion criteria1. Evidence (laboratory and clinical history) of pre-existing non-tuberculosis disease likely to affect the response to, or assessment of treatment effects or represent contraindications to the study medication:
1.1. Diabetes mellitus
1.2. Liver impairment (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] greater than 2 x the upper limit of normal value)
1.3. Renal failure (serum creatinine greater than 2.0 mg/dl)
1.4. Epilepsy
1.5. Optical neuritis
1.6. Pancreatitis (lipase greater than 140 U/l)
1.7. Neutropenia (total neutrophil count less than 1200 cells/l)
1.8. Severe anaemia (haemoglobin less than 6.9 g/dl)
1.9. Any other condition that in the view of the country Principal Investigator represents a contraindication to the study medication
2. Mental illness (clinical suspicion of schizophrenia, manic-depressive illness, dementia)
3. Stage IV disease (according to World Health Organization [WHO] staging system)
4. Weight below 30 kg
5. Moribund or clinical evidence of severe illness
Date of first enrolment30/05/2006
Date of final enrolment30/06/2014

Locations

Countries of recruitment

  • South Africa
  • Switzerland
  • Tanzania
  • Uganda
  • Zambia

Study participating centre

World Health Organization
Geneva-27
CH-1211
Switzerland

Sponsor information

World Health Organization (WHO) (Switzerland)
Research organisation

20 Avenue Appia
Geneva 27
CH-1211
Switzerland

Phone +41 (0)22 791 4478
Email onyebujohp@who.int
Website http://www.who.int
ROR logo "ROR" https://ror.org/01f80g185

Funders

Funder type

Research organisation

World Health Organization (WHO) (Switzerland)
Private sector organisation / International organizations
Alternative name(s)
منظمة الصحة العالمية, 世界卫生组织, Всемирная организация здравоохранения, Organisation mondiale de la Santé, Organización Mundial de la Salud, WHO, 世卫组织, ВОЗ, OMS
Location
Switzerland
US Agency for International Development (USAID) (USA)

No information available

GlaxoSmithKline (GSK) - drug supply

No information available

Merck & Co Inc. - drug supply

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/07/2014 Yes No