Condition category
Infections and Infestations
Date applied
29/03/2006
Date assigned
29/03/2006
Last edited
30/09/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Philip Onyebujoh

ORCID ID

Contact details

World Health Organization
20 Avenue Appia
Geneva-27
CH-1211
Switzerland
+41 (0)22 791 4478
onyebujohp@who.int

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

South Africa (A50560), Zambia (A50636), Uganda (A30224) and Tanzania (A30213)

Study information

Scientific title

Acronym

TB-HAART

Study hypothesis

That 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

Ethics approval received on the 17/08/2005.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) co-infections

Intervention

Placebo 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 type

Drug

Phase

Not Specified

Drug names

Highly Active Anti-Retroviral Therapy (HAART)

Primary outcome measures

The 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 measures

1. 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 trial start date

30/05/2006

Overall trial end date

30/06/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. 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.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1900

Participant exclusion criteria

1. 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

Recruitment start date

30/05/2006

Recruitment end date

30/06/2014

Locations

Countries of recruitment

South Africa, Tanzania, Uganda, Zambia

Trial participating centre

World Health Organization
Geneva-27
CH-1211
Switzerland

Sponsor information

Organisation

World Health Organization (WHO) (Switzerland)

Sponsor details

20 Avenue Appia
Geneva 27
CH-1211
Switzerland
+41 (0)22 791 4478
onyebujohp@who.int

Sponsor type

Research organisation

Website

http://www.who.int

Funders

Funder type

Research organisation

Funder name

World Health Organization (WHO) (Switzerland)

Alternative name(s)

WHO

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

Switzerland

Funder name

US Agency for International Development (USAID) (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

GlaxoSmithKline (GSK) - drug supply

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Merck & Co Inc. - drug supply

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24810491

Publication citations

  1. Results

    Mfinanga SG, Kirenga BJ, Chanda DM, Mutayoba B, Mthiyane T, Yimer G, Ezechi O, Connolly C, Kapotwe V, Muwonge C, Massaga J, Sinkala E, Kohi W, Lyantumba L, Nyakoojo G, Luwaga H, Doulla B, Mzyece J, Kapata N, Vahedi M, Mwaba P, Egwaga S, Adatu F, Pym A, Joloba M, Rustomjee R, Zumla A, Onyebujoh P, Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial., Lancet Infect Dis, 2014, 14, 7, 563-571, doi: 10.1016/S1473-3099(14)70733-9.

Additional files

Editorial Notes