A Pragmatic Trial With Optimized Dose of Rifampicin and Moxifloxacin for the Treatment of Drug Susceptible Pulmonary Tuberculosis
NCT ID: NCT05575518
Last Updated: 2023-08-25
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
414 participants
INTERVENTIONAL
2023-08-11
2026-03-31
Brief Summary
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This protocol seeks to conduct the TB clinical trial combining the 8-methoxyfluroquinolone and optimised dose of rifamycing to address two questions. The first is to confirm the non-inferiority of a four-month optimised dose rifamycin and moxifloxacin-based regimen amongst African TB patient populations with high rates of co-incident HIV. Secondly, we seek to establish that the rifamycin of choice in potent 4-month anti-TB treatments could be rifampicin as this will be more rapidly up-scalable for public health impact.
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Detailed Description
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Primary effectiveness objective: To evaluate whether one or both of two experimental regimens based on optimised dose rifampicin with or without moxifloxacin and given for 16 weeks are non-inferior to standard treatment for drug-susceptible tuberculosis given for 26 weeks, as assessed by patient survival, free of tuberculosis 12 months after initiation of therapy.
Primary safety objective: To evaluate whether one or both of two experimental regimens based on optimised dose rifampicin with or without moxifloxacin and given for 16 weeks are as safe and tolerable as standard treatment for drug-susceptible tuberculosis given for 26 weeks, as assessed by the frequency of Adverse Events (AEs) of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 severity or higher.
Participants will be individuals with bacteriological confirmed pulmonary TB aged 18 years or above, with or without HIV co-infection in Gabon, Malawi, Mozambique and Tanzania. The trial sites are also established members of the PanACEA / SimpliciTB group including the Centre de Recherches Médicales de Lambaréné (CERMEL)-Gabon, the Helse Nord Tuberculosis Initiative (HNTI) at Kamuzu University of Health Sciences (KUHES)-Malawi and the Polana Caniço Health Research and Training Center (CISPOC) at the Instituto Nacional de Saúde (INS)-Mozambique and the Kibong'oto Infectious Diseases Hospital-Tanzania.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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No intervention
Standard of care according to the National TB Programmes which is a weight-banded rifampicin, isoniazid, pyrazinamide, and ethambutol for weeks 0-8 followed by rifampicin and isoniazid for weeks 9-26.
No interventions assigned to this group
Experimental Arm 1
Optimised dose of rifampicin. The rifampicin 35mg/kg alongside standard weight-banded doses of isoniazid, pyrazinamide, and ethambutol, once daily
Optimised rifamycin
optimised dose rifampicin with or without moxifloxacin
Experimental Arm 2
Optimised dose of rifampicin and moxifloxacin. The rifampicin 35mg/kg and moxifloxacin 400mg alongside standard weight-banded doses of isoniazid and pyrazinamide, once daily.
Optimised rifamycin
optimised dose rifampicin with or without moxifloxacin
Interventions
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Optimised rifamycin
optimised dose rifampicin with or without moxifloxacin
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. The patient has a diagnosis of pulmonary TB established by Xpert MTB/RIF® result which confirms "low" "medium" or "high" level detection of M tuberculosis and does not detect rifampicin resistance.
1. If the patient has been referred from a clinic at which the pre-screening clinical diagnostic test for TB was an Xpert MTB/RIF® assay done at the trial laboratory, and the full read-out of that result is available, the test does not need to repeated to confirm eligibility.
2. If the patient has been referred from a clinic at which the pre-screening clinical diagnostic test for TB was an Xpert MTB/RIF® assay done at a non-trial laboratory, but the full read-out of that result is available, the test does not need to repeated to confirm eligibility.
3. If the patient has been referred to the study from a clinic from which the full pre-screening clinical diagnostic Xpert MTB/RIF® test result is unavailable, a repeat Xpert MTB/RIF® assay should be performed by the study laboratory to confirm eligibility before recruitment.
3. The patient should be aged ≥ 18 years on the day of providing informed consent.
4. The patient has a body weight in light clothing and without shoes of at least 35kg.
5. Female patients of child-bearing potential must have a negative urine or serum pregnancy test ≤ 7 days prior to screening, and consent to practice an effective method of contraception until completion of therapy.
6. The patient must have a verifiable residence location and telephone number that is accessible if necessary for contact during follow-up.
Exclusion Criteria
1. There is concern about any circumstances that raise concern about free, informed consent to study participation.
2. The patient's pre-screening or screening Xpert MTB/RIF® assay result is "negative","trace", or "very low" positive.
3. At least one M tuberculosis isolate, either cultured or detected through molecular assays from sputum obtained from the patient prior to treatment initiation is found to be resistant to one or more of: rifampicin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones (late exclusion).
4. The patient is in poor general condition where delay in treatment cannot be tolerated, or death within three months is likely, as assessed by the investigator.
5. The patient had a nose/throat swab which was positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), on Polymerase Chain Reaction (PCR) or a rapid diagnostic test ≤ 14 days preceding study recruitment.
6. The patient is pregnant or breast-feeding (female patients only).
7. The patient is unable to take oral medications.
8. The patient has received any investigational drug in the past three months.
9. The patient has received more than five days of treatment directed against active tuberculosis ≤ 6 months preceding initiation of study drugs.
10. The patient has known intolerance to any of the study drugs, or conditions for which they are contra-indicated.
11. The patient is unwilling, or unable to adhere to requirements regarding restricted use of other medications during the study. Restricted medications will include medications which prolong the QTc interval, and CYP450 inhibitors or inducers.
12. The patient is due to initiate, or requires continuation of, non-efavirenz, non-dolutegravir-based anti-retroviral therapy for HIV infection.
13. The patient has decompensated liver disease and/or aminotransaminases \>3x upper limit of normal (ULN), serum total bilirubin level \>1.5x ULN or serum/plasma creatinine level \>x2 ULN.
14. The patient has a baseline QTc interval of \>450ms.
15. The patient is being, or about to be, treated for malaria.
16. The patient has other medical conditions that, in the investigator's judgement, make study participation not in the individual's best interest.
18 Years
65 Years
ALL
No
Sponsors
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University of St Andrews
OTHER
Radboud University Medical Center
OTHER
Stellah Mpagama
OTHER_GOV
Responsible Party
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Stellah Mpagama
Director of Research
Locations
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Kibong'oto Infectious Diseases Hospital
Moshi, Kilimanjaro, Tanzania
Countries
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Central Contacts
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Facility Contacts
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References
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World Health Organization. Global Tuberculosis Report 2021. World Health Organisation 2021.https://www.who.int/publications/i/item/9789240037021
World Health Organisation. WHO End TB Strategy: Global strategy and targets for tuberculosis prevention, care and control after 2015. World Health Organization 2021. https://www.who.int/tb/strategy/End_TB_Strategy.pdf
Pai M, Kasaeva T, Swaminathan S. Covid-19's Devastating Effect on Tuberculosis Care - A Path to Recovery. N Engl J Med. 2022 Apr 21;386(16):1490-1493. doi: 10.1056/NEJMp2118145. Epub 2022 Jan 5. No abstract available.
Boeree MJ, Diacon AH, Dawson R, Narunsky K, du Bois J, Venter A, Phillips PP, Gillespie SH, McHugh TD, Hoelscher M, Heinrich N, Rehal S, van Soolingen D, van Ingen J, Magis-Escurra C, Burger D, Plemper van Balen G, Aarnoutse RE; PanACEA Consortium. A dose-ranging trial to optimize the dose of rifampin in the treatment of tuberculosis. Am J Respir Crit Care Med. 2015 May 1;191(9):1058-65. doi: 10.1164/rccm.201407-1264OC.
Te Brake LHM, de Jager V, Narunsky K, Vanker N, Svensson EM, Phillips PPJ, Gillespie SH, Heinrich N, Hoelscher M, Dawson R, Diacon AH, Aarnoutse RE, Boeree MJ; PanACEA Consortium. Increased bactericidal activity but dose-limiting intolerability at 50 mg.kg-1 rifampicin. Eur Respir J. 2021 Jul 8;58(1):2000955. doi: 10.1183/13993003.00955-2020. Print 2021 Jul.
Boeree MJ, Heinrich N, Aarnoutse R, Diacon AH, Dawson R, Rehal S, Kibiki GS, Churchyard G, Sanne I, Ntinginya NE, Minja LT, Hunt RD, Charalambous S, Hanekom M, Semvua HH, Mpagama SG, Manyama C, Mtafya B, Reither K, Wallis RS, Venter A, Narunsky K, Mekota A, Henne S, Colbers A, van Balen GP, Gillespie SH, Phillips PPJ, Hoelscher M; PanACEA consortium. High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial. Lancet Infect Dis. 2017 Jan;17(1):39-49. doi: 10.1016/S1473-3099(16)30274-2. Epub 2016 Oct 26.
Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HTT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. N Engl J Med. 2021 May 6;384(18):1705-1718. doi: 10.1056/NEJMoa2033400.
WHO consolidated guidelines on tuberculosis: Module 4: Treatment - Drug-susceptible tuberculosis treatment [Internet]. Geneva: World Health Organization; 2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK581329/
Other Identifiers
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OptiRiMoxTB-01
Identifier Type: -
Identifier Source: org_study_id
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