Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis

RIFASHORT Study Group; Amina Jindani; Daniel Atwine; Daniel Grint; Boubacar Bah; Jack Adams; Eduardo Rómulo Ticona; Bhabana Shrestha; Tefera Agizew; Saeed Hamid; Bushra Jamil; Adolf Byamukama; Keneth Kananura; Ivan Mugisha Taremwa; Maryline Bonnet; Lansana Mady Camara; Oumou Younoussa Bah-Sow; Kindy Sadio Bah; Nene Mamata Bah; Maimouna Sow; César Eduardo Ticona Huaroto; Raquel Mugruza Pineda; Bijesh Tandukar; Bijendra Bhakta Raya; Neko Shrestha; Anikie Mathoma; Unami P Mathebula-Modongo; Joyce Basotli; Muhammad Irfan; Dilshad Begum; Jonathan Decker; Thomas S. Harrison; et al

doi:10.1056/EVIDoa2300054

Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis

RIFASHORT Study Group, Amina Jindani, Daniel Atwine, Daniel Grint, Boubacar Bah, Jack Adams, Eduardo Rómulo Ticona, Bhabana Shrestha, Tefera Agizew, Saeed Hamid, Bushra Jamil, Adolf Byamukama, Keneth Kananura, Ivan Mugisha Taremwa, Maryline Bonnet, Lansana Mady Camara, Oumou Younoussa Bah-Sow, Kindy Sadio Bah, Nene Mamata Bah, Maimouna SowCésar Eduardo Ticona Huaroto, Raquel Mugruza Pineda, Bijesh Tandukar, Bijendra Bhakta Raya, Neko Shrestha, Anikie Mathoma, Unami P Mathebula-Modongo, Joyce Basotli, Muhammad Irfan, Dilshad Begum, Jonathan Decker, Thomas S. Harrison^*, et al

^*Corresponding author for this work

Bristol Medical School (PHS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

Abstract

Background:
Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens.

Methods:
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]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first.

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.

Conclusions:
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 tuberculosis. (Funded by the MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme; ClinicalTrials.gov number, NCT02581527.)

Original language	English
Article number	EVIDoa2300054
Number of pages	12
Journal	NEJM Evidence
Volume	2
Issue number	9
DOIs	https://doi.org/10.1056/EVIDoa2300054
Publication status	Published - 22 Aug 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Humans
Rifampin/adverse effects
Antitubercular Agents/adverse effects
Isoniazid/therapeutic use
Drug Therapy, Combination
Tuberculosis, Pulmonary/chemically induced

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10.1056/EVIDoa2300054

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RIFASHORT Study Group, Jindani, A., Atwine, D., Grint, D., Bah, B., Adams, J., Ticona, E. R., Shrestha, B., Agizew, T., Hamid, S., Jamil, B., Byamukama, A., Kananura, K., Mugisha Taremwa, I., Bonnet, M., Camara, L. M., Bah-Sow, O. Y., Bah, K. S., Bah, N. M., ... al, E. (2023). Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis. NEJM Evidence, 2(9), Article EVIDoa2300054. https://doi.org/10.1056/EVIDoa2300054

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title = "Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis",

abstract = "Background: Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens. Methods: 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]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first. 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. Conclusions: 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 tuberculosis. (Funded by the MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme; ClinicalTrials.gov number, NCT02581527.)",

keywords = "Humans, Rifampin/adverse effects, Antitubercular Agents/adverse effects, Isoniazid/therapeutic use, Drug Therapy, Combination, Tuberculosis, Pulmonary/chemically induced",

author = "\{RIFASHORT Study Group\} and Amina Jindani and Daniel Atwine and Daniel Grint and Boubacar Bah and Jack Adams and Ticona, \{Eduardo R{\'o}mulo\} and Bhabana Shrestha and Tefera Agizew and Saeed Hamid and Bushra Jamil and Adolf Byamukama and Keneth Kananura and \{Mugisha Taremwa\}, Ivan and Maryline Bonnet and Camara, \{Lansana Mady\} and Bah-Sow, \{Oumou Younoussa\} and Bah, \{Kindy Sadio\} and Bah, \{Nene Mamata\} and Maimouna Sow and \{Ticona Huaroto\}, \{C{\'e}sar Eduardo\} and \{Mugruza Pineda\}, Raquel and Bijesh Tandukar and Raya, \{Bijendra Bhakta\} and Neko Shrestha and Anikie Mathoma and Mathebula-Modongo, \{Unami P\} and Joyce Basotli and Muhammad Irfan and Dilshad Begum and Jonathan Decker and Harrison, \{Thomas S.\} and et al",

year = "2023",

month = aug,

day = "22",

doi = "10.1056/EVIDoa2300054",

language = "English",

volume = "2",

journal = "NEJM Evidence",

issn = "2766-5526",

publisher = "Massachussetts Medical Society",

number = "9",

}

RIFASHORT Study Group, Jindani, A, Atwine, D, Grint, D, Bah, B, Adams, J, Ticona, ER, Shrestha, B, Agizew, T, Hamid, S, Jamil, B, Byamukama, A, Kananura, K, Mugisha Taremwa, I, Bonnet, M, Camara, LM, Bah-Sow, OY, Bah, KS, Bah, NM, Sow, M, Ticona Huaroto, CE, Mugruza Pineda, R, Tandukar, B, Raya, BB, Shrestha, N, Mathoma, A, Mathebula-Modongo, UP, Basotli, J, Irfan, M, Begum, D, Decker, J, Harrison, TS & al, E 2023, 'Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis', NEJM Evidence, vol. 2, no. 9, EVIDoa2300054. https://doi.org/10.1056/EVIDoa2300054

TY - JOUR

T1 - Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis

AU - RIFASHORT Study Group

AU - Jindani, Amina

AU - Atwine, Daniel

AU - Grint, Daniel

AU - Bah, Boubacar

AU - Adams, Jack

AU - Ticona, Eduardo Rómulo

AU - Shrestha, Bhabana

AU - Agizew, Tefera

AU - Hamid, Saeed

AU - Jamil, Bushra

AU - Byamukama, Adolf

AU - Kananura, Keneth

AU - Mugisha Taremwa, Ivan

AU - Bonnet, Maryline

AU - Camara, Lansana Mady

AU - Bah-Sow, Oumou Younoussa

AU - Bah, Kindy Sadio

AU - Bah, Nene Mamata

AU - Sow, Maimouna

AU - Ticona Huaroto, César Eduardo

AU - Mugruza Pineda, Raquel

AU - Tandukar, Bijesh

AU - Raya, Bijendra Bhakta

AU - Shrestha, Neko

AU - Mathoma, Anikie

AU - Mathebula-Modongo, Unami P

AU - Basotli, Joyce

AU - Irfan, Muhammad

AU - Begum, Dilshad

AU - Decker, Jonathan

AU - Harrison, Thomas S.

AU - al, et

PY - 2023/8/22

Y1 - 2023/8/22

N2 - Background: Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens. Methods: 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]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first. 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. Conclusions: 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 tuberculosis. (Funded by the MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme; ClinicalTrials.gov number, NCT02581527.)

AB - Background: Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens. Methods: 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]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first. 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. Conclusions: 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 tuberculosis. (Funded by the MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme; ClinicalTrials.gov number, NCT02581527.)

KW - Humans

KW - Rifampin/adverse effects

KW - Antitubercular Agents/adverse effects

KW - Isoniazid/therapeutic use

KW - Drug Therapy, Combination

KW - Tuberculosis, Pulmonary/chemically induced

U2 - 10.1056/EVIDoa2300054

DO - 10.1056/EVIDoa2300054

M3 - Article (Academic Journal)

C2 - 38320155

SN - 2766-5526

VL - 2

JO - NEJM Evidence

JF - NEJM Evidence

IS - 9

M1 - EVIDoa2300054

ER -

Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis

Abstract

UN SDGs

Keywords

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