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

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 1250

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

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)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Combined rate of failure at the end of treatment and relapse, measured at 18 months <br>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 <br>3. Occurrence of serious adverse events at any time during chemotherapy, recorded as they present themselves throughout the course of the trial<br><br>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

Name	Time	Method
1. Sputum culture results at two months after the initiation of chemotherapy, measured at all visits<br>2. Rate of completion of chemotherapy according to the protocol, measured at all visits<br>3. Number of observed doses of chemotherapy ingested, measured at all visits<br>4. Any adverse events, recorded as they present themselves throughout the course of the trial