InterTB Trials and Studies

Key information

• Status: Published
• Phase: III
• Dates: August 2023
• Chief Investigator: Dr Amina Jindani
• Key Collaborators: Daniel Atwine, Ph.D.,2,3 Daniel Grint, Ph.D.,4 Boubacar Bah, M.D.,5 Jack Adams, B.Sc.,1 Eduardo Rŏmulo Ticona, Ph.D., 6 Bhabana Shrestha, M.D.,7 Tefera Agizew, Ph.D.,8 Saeed Hamid, F.R.C.P.,9 Bushra Jamil, F.R.C.P.,9 Adolf Byamukama, M.D.,2 Keneth Kananura, M.Med.,2 Ivan Mugisha Taremwa, M.Sc.,2 Maryline Bonnet, Ph.D.,2,10 Lansana Mady Camara, M.D.,5 Oumou Younoussa Bah-Sow, Ph.D.,5 Kindy Sadio Bah, M.D.,5 Nene Mamata Bah, Ph.D.,5 Maimouna Sow, D.M.L.T.,5 César Eduardo Ticona Huaroto, M.D.,6 Raquel Mugruza Pineda, B.Sc.,6 Bijesh Tandukar, M.Sc.,7 Bijendra Bhakta Raya, B.Sc.,7 Neko Shrestha, M.B.B.S.,7 Anikie Mathoma, M.P.H.,8= Unami P. Mathebula-Modongo, Ph.D.,8 Joyce Basotli, B.Tech.,8 Muhammad Irfan, F.R.C.P.,9 Dilshad Begum, M.Sc.,9 Ammara Muzammil, D.Pharm.,9 Imran Ahmed, M.D.,9 Rumina Hasan, F.R.C.Path.,9 Marcos V. Burgos, M.D.,11 Faisal Sultan, F.R.C.P.,12 Mariam Hassan, M.Sc.,12 Iqra Masood, M.Phil.,12 Claire Robb, B.Sc.,1 Jonathan Decker, M.Sc.,13 Sisa Grubnic, F.R.C.R.,14 Philip D. Butcher, Ph.D.,1 Adam Witney, Ph.D.,1 Jasvir Dhillon, Ph.D.,1 Tulika Munshi, Ph.D.,1 Katherine Fielding, Ph.D.,4 Thomas S. Harrison, M.D.,1,14,1
• Locations: [1] Institute for Infection and Immunity, St. George’s, University of London, United Kingdom [2] Epicentre/Mbarara Research Base, Mbarara. Uganda [3] Mbarara University of Science and Technology, Mbarara, Uganda. [4] London School of Hygiene and Tropical Medicine, London, United Kingdom [5] Centre Hospitalier Universitaire Ignace Deen, Conakry, Guinea [6] Hospital Nacional Dos de Mayo, Universidad Nacional Mayor de San Marcos, Lima,Peru [7] German Nepal TB Project (GENETUP)/ Nepal Anti TB Association ( NATA), Kathmandu, Nepal [8] University of Botswana, Gaborone, Botswana [9] Aga Khan University Hospital, Karachi, Pakistan [10] University of Montpellier, TransVIHMI, IRD, INSERM, Montpellier France [11] Division of Infectious Diseases, University of New Mexico, Albuquerque, NM, USA [12] Shaukat Khanum Research Centre and Cancer Hospital, Lahore [13] Department of Respiratory Sciences, University of Leicester, Leicester, UK [14] Clinical Academic Group in Infection and Immunity, St George’s University Hospitals NHS Foundation Trust, London, UK [15] MRC Centre for Medical Mycology, University of Exeter, Exeter, UK
• Funding: MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme

Project summary

We randomly assigned adults who were given a diagnosis of rifampicin-susceptible pulmonary tuberculosis to a 6-month control regimen, a similar 4-month regimen of rifampicin at 1200 mg/d (study regimen 1 [SR1]), or a 4-month regimen of rifampicin at 1800 mg/d (study regimen 2 [SR2]). The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline.

Results

Between January 2017 and December 2020, 672 patients were enrolled in six countries, including 191 in the control group, 192 in the SR1 group, and 195 in the SR2 group. Noninferiority was not shown. Favorable responses rates were 93, 90, and 87% in the control, SR1, and SR2 groups, respectively, for a country-adjusted absolute risk difference of 6.3 percentage points (90% confidence interval, 1.1 to 11.5) comparing SR2 with the control group. The proportions of participants experiencing a grade 3 or 4 adverse event were 4.0, 4.5, and 4.4% in the control, SR1, and SR2 groups, respectively. In conclusion: Four-month high-dose rifampicin regimens did not have dose-limiting toxicities or side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen for treatment of pulmonary tuberculosi.

Read the published results.

Key information

• Status: Published
• Phase: III
• Dates: August 2008 – Feb 2013
• Chief Investigator: Dr Amina Jindani
• Key Collaborators: MRC CTU
• Locations: South Africa, Zambia, Botswana and Zimbabwe
• Funding: EDCTP

Project summary

In this trial, we assessed whether two newer drugs (rifapentine and moxifloxacin), when given together, can shorten or simplify treatment duration in order to improve overall patient adherence and therefore outcome.

This international, multicentre, controlled clinical trial assessed two different treatment regimens against the standard six month treatment for TB. One arm had a duration of four months and included the two newer drugs given on a twice weekly basis in the last two months. The other had a duration of six months with the two newer drugs given once-weekly in the last four months.

Results

The four-month regimen with a twice-weekly continuation phase gave disappointing results; relapse rates were significantly higher than those in the six-month control regimen.

However, the six-month regimen was as effective as the control regimen. It offers the prospect of a new regimen requiring considerably fewer days of treatment in the two month continuation phase, which was administered once-weekly, as compared to the control regimen, which was given daily throughout the treatment.

This six-month regimen could have an impact on the burden for both patients and National TB programs as it requires less treatment and administration time.

Read the published results.

Key information

• Status: Published
• Phase: IIB
• Dates: Feb 2011 – May 2013
• Chief Investigator: Dr Amina Jindani
• Locations: Uganda, Bolivia, Nepal
• Funding: St George's, University of London and Epicentre-MSF (Uganda)

Project summary

The main aim of the RIFATOX trial was to evaluate whether increasing the dose of one of the drugs used to treat TB, rifampicin, is safe and tolerated by patients.

The trial consisted of three arms, assessing the standard treatment of six months duration against two trial arms of increased rifampicin for four months followed by standard treatment for two months. In one trial arm rifampicin was increased to 15 mg/kg daily and in the other arm to 20 mg/kg daily.

Results

The trial concluded that the increased dose of rifampicin was safe and well tolerated. The trial has been used to inform the development of RIFASHORT (see above).

Read the published results.