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Evaluation of metformin in combination with rifampicin containing antituberculosis therapy in patients with new, smear-positive pulmonary tuberculosis (METRIF): study protocol for a randomised clinical trial
  1. Chandrasekaran Padmapriyadarsini1,
  2. Perumal K Bhavani1,
  3. Mohan Natrajan1,
  4. Chinnayan Ponnuraja1,
  5. Hemanth Kumar1,
  6. Sivaramakrishnan N Gomathy1,
  7. Randeep Guleria2,
  8. Shaheed M Jawahar3,
  9. Manjula Singh4,
  10. Tanjore Balganesh3,
  11. Soumya Swaminathan4,5
  1. 1 ICMR-National Institute for Research in Tuberculosis, Chennai, India
  2. 2 All India Institute of Medical Sciences, New Delhi, India
  3. 3 Open Source Pharma Foundation, Chennai, India
  4. 4 Indian Council of Medical Research-India TB Research Consortium, New Delhi, India
  5. 5 World Health Organisation, Geneva, Switzerland
  1. Correspondence to Dr Chandrasekaran Padmapriyadarsini; pcorchids{at}gmail.com

Abstract

Introduction Shorter duration of treatment for the management of drug-susceptible pulmonary tuberculosis (TB) would be a significant improvement in the care of patients suffering from the disease. Besides newer drugs and regimens, other modalities like host-directed therapy are also being suggested to reach this goal. This study’s objective is to assess the efficacy and safety of metformin-containing anti-TB treatment (ATT) regimen in comparison to the standard 6-month ATT regimen in the treatment of patients with newly diagnosed sputum smear-positive drug-sensitive pulmonary TB.

Methods and analysis We are conducting a multicentric, randomised open-label controlled clinical trial to achieve the study objective. The intervention group will receive isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) along with 1000 mg of daily metformin (Met) for the first 2 months while the control group will receive only HRZE. After 2 months, both the groups will receive HRE daily for 4 months. The primary endpoint is time to sputum culture conversion. Secondary endpoints will include time to detection of Mycobacterium tuberculosis in sputum, pharmacokinetics and pharmacogenomics of study drugs, drug–drug interactions, safety and tolerability of the various combinations and measurement of autophagy and immune responses in the study participants.

Ethics and dissemination The ethics committee of the participating institutes have approved the study. Results from this trial will contribute to evidence towards constructing a shorter, effective and safe regimen for patients with TB. The results will be shared widely with the National Programme managers, policymakers and stakeholders through open access publications, dissemination meetings, conference abstracts and policy briefs. This is expected to provide a new standard of care for drug-sensitive patients with pulmonary TB who will not only reduce the number of clinic visits and lost to follow-up of patients from treatment but also reduce the burden on the healthcare system.

Trial registration number CTRI/2018/01/011176; Pre-results.

  • tuberculosis
  • respiratory infections
  • clinical trials
  • public health

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors CP and SS: conceived and designed the study. CP, PKB, MN, CPr, HK, NSG, RG, SJ, TB, SS: development and writing of the study protocol and this manuscript.

  • Funding India TB Research Consortium, Indian Council of Medical Research, New Delhi and Open Source Pharma Foundation, Bangalore, India provided funding for the study. Trial Sponsor: Indian Council of Medical Research – National Institute for Research in Tuberculosis.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent for publication Not required.

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