Condition category
Infections and Infestations
Date applied
12/10/2010
Date assigned
09/11/2010
Last edited
29/03/2011
Prospective/Retrospective
Retrospectively 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 Amina Jindani

ORCID ID

Contact details

St George's University of London
Infection and Immunity Research Centre
Cranmer Terrace
London
SW17 0RE
United Kingdom
+44 (0)20 8725 2810
ajindani@sgul.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

version 2.1

Study information

Scientific title

An international multicentre controlled clinical trial to evaluate the toxicity of high dose rifampicin in the treatment of pulmomary tuberculosis (RIFATOX)

Acronym

RIFATOX

Study hypothesis

The current treatment of tuberculosis involves taking drugs daily for 6 or 8 months. Although the drugs are free to patients in low income countries, this still involves a substantial cost, in terms of time and administration, to both the patient and the treatment services. If the length of treatment could be shortened to 3, or even, 4 months, this would be of great benefit to the patients and the treatment services. A shorter treatment could also result in greater cure rates and, perhaps, a reduction in the emergence of resistance to the drugs.

One of the drugs given in treatment is called rifampicin. Laboratory experiments suggest that increasing the dose of rifampicin results in a greater killing of the tubercle bacillus both in liquid suspensions and in animals.

In this trial, we are assessing whether giving an increased dose of rifampicin to patients receiving the standard treatment for tuberculosis is safe and does not result in greater bad effects from the higher dose. If it is found to be safe, another trial would be carried out to see if the increased dose can increase the elimination of the tubercle bacillus from the lungs and if so, whether, eventually, the treatment can be shortened to 3, or even, 4 months.

Ethics approval

1. UK:
1.1. The Oxford Tropical Research Ethics Committee (OXTREC) approved on the 2nd of August 2010 (ref: 31-01)
1.2. The St. George's University of London, R&D Office approved on the 20th of September 2010 (ref: 10.005)
2. Bolivia:
2.1. The Ministry of Health and Sports (Ministerio de Salud y Deportes) approved in April 2010 (ref: MSD/DESP./0733/2010)
2.2. The Commission for Ethics of Investigations (Comision de Ethica de la Investigation) approved on the 19th of July 2010
3. Nepal:
The National Health Research Council approved on the 15th of April 2010 (ref: 1192)
4. India:
Approval pending at time of registration

Study design

An open-label 3-arm trial to compare a standard control regimen with two alternative treatment regimens for the treatment of tuberculosis (TB).

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details below to request a patient information sheet

Condition

Infectious Diseases; Tuberculosis

Intervention

All patients enrolled will receive treatment for 6 months. The duration of the study will be the first 4 months of treatment. For the last 2 months of treatment, the patients will be transferred to the National Treatment Programme to complete 6 months.
Control Regimen : 2 months of daily ethambutol, isoniazid, rifampicin, and pyrazinamide followed by 4 months of daily isoniazid and rifampicin (2EHRZ/4HR)A.
Study Regimen 1: The regimen as above but with an increase in the dose of rifampicin to 15mg/kg body weight daily for the first 4 months. (2EHR15Z/2HR15/2HR)B For the first 4 months, the dose of rifampicin will be 15mg/kg.
Study Regimen 2: The regimen as above but with an increase in the dose of rifampicin to
20mg /kg body weight daily for the first 4 months. (2EHR20Z/2HR20/2HR)C For the first 4 months, the dose of rifampicin will be 20mg/kg.

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measures

Occurrence of grade 3 or 4 adverse events at any time during chemotherapy.

Secondary outcome measures

1. Culture conversion at the end of 8 weeks of chemotherapy
2. Per protocol analysis of the primary outcome.
3. Any adverse event graded according to the modified Division of Aids (DAIDS) criteria
4. Rate of completion of chemotherapy according to the protocol
5. Number of observed doses of chemotherapy ingested

Overall trial start date

01/10/2010

Overall trial end date

01/10/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Newly diagnosed pulmonary tuberculosis
2. Two sputum specimens positive for tubercle bacilli on direct smear microscopy
3. No previous anti-tuberculosis chemotherapy
4. Aged 18 years and over
5. A firm home address that is readily accessible for visiting and be intending to remain there or within the recruitment area for the entire treatment period
6. Agree to participate in the study and to give a sample of blood for HIV testing
7. Pre-menopausal women must be using a barrier form of contraception or be surgically sterilised or have an interuterine contraceptive device (IUCD) in place for the duration of the treatment phase

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

300

Participant exclusion criteria

1. Has any condition (except HIV infection) that may prove fatal during the study period
2. Has 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-retro viral treatment (ART) at diagnosis
8. Haemoglobin <7g/l
9. Asparate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 5 times the upper limit of normal (ULN) for that laboratory
10. Creatinine clearance of < 30mls/min
Calculated as ((140-age) x weight x 1.23 x (0.85 if female))/Creat[micromol/l)
11. Has glucose in urine
12. Is HIV positive with a CD4 count of less than 350/mm3
13. Weight < 35kg

Recruitment start date

01/10/2010

Recruitment end date

01/10/2012

Locations

Countries of recruitment

Bolivia, India, Nepal

Trial participating centre

St George's University of London
London
SW17 0RE
United Kingdom

Sponsor information

Organisation

St George's University of London (UK)

Sponsor details

Cranmer Terrace
London
SW17 0RE
United Kingdom
+44 (0)20 8725 2810
ajindani@sgul.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Not defined

Funder name

Pending at time of registration

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

Publication citations

Additional files

Editorial Notes