Plain English Summary
Background and study aims
Within the UK, completion rates for latent tuberculosis infection (LTBI) treatment regimens are known to be poor. A recent paper described a novel LTBI treatment regimen of Rifapentine/Isoniazid with high completion rates. Our pilot study will compare completion rates between this novel regimen and a Rifinah regimen and will provide useful data to inform future practice. The value for money of this approach will be assessed.
Who can participate?
Participants must be male or non-pregnant, non-nursing, females between 16 years of age and 65 years. They must test positive for LTBI, but not have active tuberculosis disease, and be willing to provide signed informed consent. Individuals allergic to the study medications, who have HIV, significant liver disease, who are high risk drinkers, who are taking medications that may interact with the study drugs and who would usually have Directly Observed Treatment (DOT) are not eligible.
What does the study involve?
Participants will be randomly allocated to either twice daily Rifinah or weekly Rifapentine and Isoniazid for three months. Treatment adherence and adverse reactions will be monitored every month through clinic appointments and for one month after treatment completion.
What are the possible benefits and risks of participating?
Participants could reduce their risk of developing active tuberculosis by being treated.
Possible side effects include hepatoxicity (damage of the liver). These would be monitored during the study and the treatment would be stopped if clinically indicated.
Where is the study run from?
University College London (UK).
When is study starting and how long is it expected to run for?
The study is expected to start in April 2013 and end in September 2015. Recruitment will take place during the first 15 months.
Who is funding the study?
Department of Health (UK)
Who is the main contact?
Professor Ibrahim Abubakar
Prof Ibrahim Abubakar
University College London
Research Department of Infection and Population Health
4th floor Mortimer Market
off Capper Street
+44 (0)20 7679 0954
The HALT LTBI study: Phase IV multi-site, unblinded, randomised trial of prophylactic Rifapentine/Isoniazid versus Rifampicin/Isoniazid (Rifinah) for latent tuberculosis infection (LTBI)
Completion rates for individuals treated with Rifapentine/Isoniazid will be higher than for those treated with Rifinah.
On 31/03/2014 the following changes were made to the trial record:
1. The anticipated start date was changed from 01/04/2013 to 01/05/2014
2. The anticipated end date was changed from 30/09/2015 to 31/05/2015
NRES Committee London, Brent, 29/11/2013, ref: 13/LO/1666
Pilot of a randomised control trial of completion of, and adverse reactions to, LTBI treatment comparing daily Rifinah for 3 months or Rifapentine/Isoniazid weekly for 3 months.
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Latent tuberculosis infection
Random allocation to either Rifinah (300mg Rifampicin plus 150mg Isoniazid, two daily) or Rifapentine and Isoniazid (3 months, 12 weekly doses); monthly follow-up for the duration of treatment and one month after treatment completion.
Primary outcome measures
1. Completion of treatment regimen
2. Associated health economics to determine cost effectiveness of the intervention
Secondary outcome measures
Adverse effects of treatment for LTBI
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Male or non-pregnant, non-nursing, female adults aged between 16 years 0 days and 64 years 364 at enrolment
2. Individuals at high risk for developing tuberculosis but without evidence of active tuberculosis. High-risk is defined on the basis of a positive Interferon Gamma Release Assay (IGRA).
3. People with no evidence of active tuberculosis who have a positive IGRA as defined above.
4. Willing and able to provide written informed consent.
Target number of participants
Participant exclusion criteria
Current exclusion criteria as of 31/03/2014:
1. Patients unable to give consent
2. Pregnant or breastfeeding women
3. Patients whose weight is under 45 kg
4. Allergies to any of the study drugs or excipients contained in preparations of these medicines
5. Patients requiring medications that cannot be safely taken with the study drugs (see Appendix 2)
6. Any medical condition deserving priority of treatment (such as: porphyria, malabsorption syndromes, Clostridium difficile-associated diarrhoea and other conditions)
7. HIV infection
8. Individuals with known liver disease, defined as LFT (ALT/AST/bilirubin) over upper limit of normal (ULN) at baseline (one abnormal value prevents the patient from participating in the study)
9. Clinical diagnosis of cirrhosis (jaundice, hematemesis, ascites or previous episodes of liver encephalopathy)
10. Chronic/active hepatitis B or hepatitis C virus infection
11. High-risk drinking, according to the Department of Health criteria (regularly drinking more than 8 units a day or 50 units a week for men; regularly drinking more than 6 units a day or 35 units a week for women)
12. Previous treatment for TB or LTBI
13. Individuals who would usually be offered LTBI treatment under Directly Observed Therapy (DOT) because of their mental or social disabilities
14. Use of another experimental investigational medicinal product that is likely to interfere with the study medication within 3 months of study enrolment
Previous exclusion criteria:
1. Females of childbearing potential must be willing to use an effective method of contraception
2. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment
3. Females must not be breastfeeding
4. Allergies to Rifapentine, Isoniazid, Rifampicin or excipients contained in the preparations of these medicines
5. Patients requiring medications that cannot be safely taken with the study drugs
6. High risk drinking, according to the Department of Health criteria
7. Those who are HIV positive
8. Individuals who already have significant liver disease
9. Those who would not be eligible for LTBI treatment under the American Thoracic Society Criteria
10. Individuals who would usually be offered LTBI treatment under Directly Observed Therapy (DOT)
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
University College London
University College London (UK)
c/o Anne Marie Downey
Joint Research Office
1st Floor Maple House (Suite A)
149 Tottenham Court Road
Department of Health Policy Research Programme (UK) ref: 015/0306
Funding Body Type
Funding Body Subtype
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