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. The aim of this study is to compare completion rates between this novel regimen and a Rifinah regimen and provide useful data to inform future practice. The value for money of this approach is assessed.
Who can participate?
Male or non-pregnant, non-nursing, females, aged between 16 and 65, who test positive for LTBI but do not have active tuberculosis disease
What does the study involve?
Participants are randomly allocated to either twice daily Rifinah or weekly Rifapentine and Isoniazid for 3 months. Treatment adherence and adverse reactions are monitored every month through clinic appointments and for 1 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 the study starting and how long is it expected to run for?
May 2014 to May 2015
Who is funding the study?
Department of Health (UK)
Who is the main contact?
Prof. Ibrahim Abubakar
i.abubakar@ucl.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof Ibrahim Abubakar
ORCID ID
http://orcid.org/0000-0002-0370-1430
Contact details
University College London
Research Department of Infection and Population Health
4th floor Mortimer Market
off Capper Street
London
WC1E 6JB
United Kingdom
+44 (0)20 7679 0954
i.abubakar@ucl.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
12/0426
Study information
Scientific title
The HALT LTBI study: Phase IV multi-site, unblinded, randomised trial of prophylactic Rifapentine/Isoniazid versus Rifampicin/Isoniazid (Rifinah) for latent tuberculosis infection (LTBI)
Acronym
Study hypothesis
Completion rates for individuals treated with Rifapentine/Isoniazid will be higher than for those treated with Rifinah.
Ethics approval
NRES Committee London, Brent, 29/11/2013, ref: 13/LO/1666
Study design
Pilot of a randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
GP practices
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Latent tuberculosis infection
Intervention
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.
Intervention type
Drug
Phase
Phase IV
Drug names
Rifampicin, isoniazid, rifapentine
Primary outcome measure
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
01/05/2014
Overall trial end date
30/06/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male or non-pregnant, non-nursing, female adults aged between 16 years 0 days and 64 years 364 days 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
100
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
01/05/2014
Recruitment end date
31/05/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University College London
London
WC1E 6JB
United Kingdom
Trial participating centre
Barts Health, Newham University Hospital
London
E13 8SL
United Kingdom
Trial participating centre
The Royal Free London NHS Foundation Trust
London
NW3 2QG
United Kingdom
Sponsor information
Organisation
University College London (UK)
Sponsor details
c/o Anne Marie Downey
Joint Research Office
1st Floor Maple House (Suite A)
149 Tottenham Court Road
London
W1T 7DN
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Department of Health Policy Research Programme (UK) ref: 015/0306
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal within one year of end of study (by 30/06/2018).
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
30/06/2018
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list