An international multicentre controlled clinical trial to evaluate high dose RIFApentine and a QUINolone in the treatment of pulmonary tuberculosis

ISRCTN	ISRCTN44153044
DOI	https://doi.org/10.1186/ISRCTN44153044
Secondary identifying numbers	N/A

Submission date: 01/05/2007
Registration date: 03/07/2007
Last edited: 03/11/2014

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

http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=49

Contact information

Dr Amina Jindani
Scientific

Centre for Infection
Department of Cellular and Molecular Medicine
St. Georges University of London
Jenner Wing
Cranmer Terrace
London
SW17 0RE
United Kingdom

Email	ajindani@sgul.ac.uk

Study information

Study design	Multicentre randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Scientific title
Study acronym	RIFAQUIN
Study hypothesis	1. Rifapentine (a rifamycin) and moxifloxacin (a quinolone) given together, will shorten the length of treatment for tuberculosis to four months and/or simplify treatment administration, i.e., given once or twice a week rather than daily 2. Doubling the dose of rifapentine will reduce the overall relapse rates and eliminate rifamycin resistance in those Human Immunodeficiency Virus (HIV) positive patients who may relapse 3. Laboratory experiments suggest that replacing isoniazid with moxifloxacin could strengthen the treatment. We are also assessing whether, by substituting moxifloxacin for isoniazid, it is possible to simplify, and even reduce the duration of, the continuation phase of treatment Please note that, as of 07/10/2008, the start date of this trial has been updated from 31/07/2008 to 15/08/2008. Please note that as of 29/04/2008 this trial record was updated. All changes can be found in the relevant section under this update date. Please also note that the anticipated start and end dates of this trial have also been updated, the previous dates were: Anticipated start date: 31/07/2007 Anticipated end date: 31/07/2009 Please note, as of 26/10/2011 updates have been made to the trial record in accordance with an amendment to the protocol. These can be found under this date of update in the relevant fields below. The anticipated end date has been extended. The previous date was 31/07/2010.
Ethics approval(s)	London-Surrey Borders Research Ethics Committee (ref: 07/Q0806/58). The most recent ethics approval for version 1.5 of the protocol was given on 17/03/2008. The protocol will also be submitted to the Medical Ethics Committee of each of the participating clinical site and/or country and enrolment to the study will start only after receiving the written agreement of the relevant body(ies).
Condition	Pulmonary tuberculosis
Intervention	Control regimen: Two months of daily ethambutol (E), isoniazid (H), rifampicin (R), and pyrazinamide (Z) followed by four months of daily isoniazid and rifampicin (2EHRZ/4HR). Study regimen one: Two months of daily ethambutol, moxifloxacin (M), rifampicin, and pyrazinamide followed by two months of twice weekly moxifloxacin and rifapentine (2EMRZ/2P2M2). Study regimen two: Two months of daily ethambutol, moxifloxacin, rifampicin, and pyrazinamide followed by four months of once weekly moxifloxacin and rifapentine (2EMRZ/4P1M1).
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Ethambutol, isoniazid, rifampicin, pyrazinamide, moxifloxacin
Primary outcome measure	1. Combined rate of failure at the end of treatment and relapse, measured at 18 months 2. Presence of Rifamycin Monoresistance (RMR) in relapse cultures of HIV infected patients, measured at 5, 6, 7, 8, 9, 10, 11, 12, 15, 18 months on the four-month arm and 7, 8, 9, 10, 11, 12, 15, 18 months on the six-month arm, plus at any unscheduled visit 3. Occurrence of serious adverse events at any time during chemotherapy, recorded as they present themselves throughout the course of the trial Added 26/10/2011: Please note, Patients will be followed up for 18 months from the commencement of chemotherapy. Follow-up visits will occur monthly until 12 months then at 15 and 18 months. However, follow-up will be stopped 12 months after the last patient has been randomised into the study; thus patients randomised in the final 6 months will have reduced follow-up.
Secondary outcome measures	1. Sputum culture results at two months after the initiation of chemotherapy, measured at all visits 2. Rate of completion of chemotherapy according to the protocol, measured at all visits 3. Number of observed doses of chemotherapy ingested, measured at all visits 4. Any adverse events, recorded as they present themselves throughout the course of the trial
Overall study start date	15/08/2008
Overall study end date	30/11/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target number of participants	1250 (Recruitment complete)
Participant inclusion criteria	1. Newly diagnosed pulmonary tuberculosis 2. Two sputum specimens positive for tubercle bacilli on direct smear microscopy 3. Either no previous anti-tuberculosis chemotherapy, or less than two weeks of previous chemotherapy 4. Aged 18 years and over 5. A firm home address that is readily accessible for visiting and be intending to remain there during the entire treatment and follow up period 6. Willing to agree to participate in the study and to give a sample of blood for HIV testing
Participant exclusion criteria	1. Has any condition (except HIV infection) that may prove fatal during the study period 2. Has Tuberculous (TB) meningitis 3. Has pre-existing non-tuberculous disease likely to prejudice the response to, or assessment of, treatment e.g., insulin-dependent diabetes, liver or kidney disease, blood disorders, peripheral neuritis 4. Is female and known to be pregnant, or breast feeding 5. Is suffering from a condition likely to lead to uncooperative behaviour such as psychiatric illness or alcoholism 6. Has contraindications to any medications in the study regimens 7. Requires Anti-Retroviral Treatment (ART) at diagnosis 8. Has a history of prolonged QTc syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone, or terfenadine during the intensive phase of TB therapy 9. Haemoglobin less than 7g/l 10. Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) greater than five times the upper range 11. Creatinine clearance of less than 30 mls/min 12. Has a history of seizures 13. Is HIV positive with a CD4 count of less than 200/mm^3 14. Weight less than 35 kg Added 26/10/2011: 15. Already receiving anti anti-retroviral therapy (ART)
Recruitment start date	15/08/2008
Recruitment end date	30/11/2012

Locations

Countries of recruitment

Botswana
England
Mozambique
South Africa
United Kingdom
Zambia
Zimbabwe

Study participating centre

Centre for Infection

London
SW17 0RE
United Kingdom

Sponsor information

St. Georges Hospital Medical School (UK)
Hospital/treatment centre

(trading as St. Georges University of London)
Centre for Infection
Department of Cellular and Molecular Medicine
Jenner Wing
Cranmer Terrace
London
SW17 0RE
England
United Kingdom

Email	ajindani@sgul.ac.uk
Website	http://www.sgul.ac.uk/
"ROR"	https://ror.org/040f08y74

Funders

Funder type

Government

European and Developing Countries Clinical Trials Partnership (EDCTP) (The Netherlands)
Private sector organisation / International organizations

Alternative name(s): Le partenariat Europe-Pays en développement pour les essais cliniques, A Parceria entre a Europa e os Países em Desenvolvimento para a Realização de Ensaios Clínicos, The European & Developing Countries Clinical Trials Partnership, European and Developing Countries Clinical Trials, EDCTP
Location: Netherlands

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2012		Yes	No
Results article	results	23/10/2014		Yes	No