Comparative evaluation of intensified short course regimen and standard regimen for adults TB meningitis: a protocol for an open label, multi-center, parallel arms, randomized controlled superiority trial (INSHORT trial).
Humans
Tuberculosis, Meningeal
/ drug therapy
Antitubercular Agents
/ administration & dosage
Multicenter Studies as Topic
India
Isoniazid
/ administration & dosage
Drug Therapy, Combination
Adult
Rifampin
/ administration & dosage
Equivalence Trials as Topic
Treatment Outcome
Drug Administration Schedule
Randomized Controlled Trials as Topic
Time Factors
Pyrazinamide
/ administration & dosage
Aspirin
/ administration & dosage
Aspirin
High-dose rifampicin
Intensified regimen
Moxifloxacin
Randomized controlled trial
Tuberculous meningitis
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
02 May 2024
02 May 2024
Historique:
received:
16
01
2024
accepted:
22
04
2024
medline:
2
5
2024
pubmed:
2
5
2024
entrez:
1
5
2024
Statut:
epublish
Résumé
Despite several incremental improvements in the management of tuberculous meningitis (TBM), the mortality rates remain high. In spite of national and international guidelines, variation in the choice, dose, and duration of drugs exist between countries and clinicians. We propose to evaluate a shorter and more effective regimen containing agents with augmented intracerebral drug exposure and anti-inflammatory approaches to improve disability-free survival among patients with TBM. Our strategy incorporates the various developments in the field of TBM over the last two decades and only few trials have evaluated a composite of these strategies in the overall outcomes of TBM. An open label, parallel arms, randomized controlled superiority trial will be conducted among 372 participants across 6 sites in India. Eligible participants will be randomly allocated in 1:1:1 ratio into one of the three arms. The intervention arm consists of 2 months of high-dose rifampicin (25 mg/kg), moxifloxacin (400 mg), pyrazinamide, isoniazid, aspirin (150 mg), and steroids followed by rifampicin, isoniazid, and pyrazinamide for 4 months. The second intervention arm includes all the drugs as per the first arm except aspirin and the patients in the control arm will receive treatment according to the National TB Elimination Program guidelines. All participants will be followed up for 1 year after the treatment. DISCUSSION: Current WHO regimens have agents with poor central nervous system drug exposure and is too long. It does not reflect the accumulating evidence in the field. We propose a comprehensive clinical trial incorporating the emerging evidence accrued over the last two decades to shorten the duration and improve the treatment outcomes. This multi-centric trial may generate crucial evidence with policy and practice implications in the treatment of TBM. Clinical Trial Registry India CTRI/2023/05/053314. Registered on 31 May 2023 ( https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODYzMzg=&Enc=&userName=CTRI/2023/05/053314 ). gov NCT05917340. Registered on 6 August 2023 ( https://classic. gov/ct2/show/NCT05917340 ). Version 1.3 dated 12 July 2023.
Sections du résumé
BACKGROUND
BACKGROUND
Despite several incremental improvements in the management of tuberculous meningitis (TBM), the mortality rates remain high. In spite of national and international guidelines, variation in the choice, dose, and duration of drugs exist between countries and clinicians. We propose to evaluate a shorter and more effective regimen containing agents with augmented intracerebral drug exposure and anti-inflammatory approaches to improve disability-free survival among patients with TBM. Our strategy incorporates the various developments in the field of TBM over the last two decades and only few trials have evaluated a composite of these strategies in the overall outcomes of TBM.
METHODS
METHODS
An open label, parallel arms, randomized controlled superiority trial will be conducted among 372 participants across 6 sites in India. Eligible participants will be randomly allocated in 1:1:1 ratio into one of the three arms. The intervention arm consists of 2 months of high-dose rifampicin (25 mg/kg), moxifloxacin (400 mg), pyrazinamide, isoniazid, aspirin (150 mg), and steroids followed by rifampicin, isoniazid, and pyrazinamide for 4 months. The second intervention arm includes all the drugs as per the first arm except aspirin and the patients in the control arm will receive treatment according to the National TB Elimination Program guidelines. All participants will be followed up for 1 year after the treatment. DISCUSSION: Current WHO regimens have agents with poor central nervous system drug exposure and is too long. It does not reflect the accumulating evidence in the field. We propose a comprehensive clinical trial incorporating the emerging evidence accrued over the last two decades to shorten the duration and improve the treatment outcomes. This multi-centric trial may generate crucial evidence with policy and practice implications in the treatment of TBM.
TRIAL REGISTRATION
BACKGROUND
Clinical Trial Registry India CTRI/2023/05/053314. Registered on 31 May 2023 ( https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODYzMzg=&Enc=&userName=CTRI/2023/05/053314 ).
CLINICALTRIALS
RESULTS
gov NCT05917340. Registered on 6 August 2023 ( https://classic.
CLINICALTRIALS
RESULTS
gov/ct2/show/NCT05917340 ).
PROTOCOL VERSION
METHODS
Version 1.3 dated 12 July 2023.
Identifiants
pubmed: 38693583
doi: 10.1186/s13063-024-08133-6
pii: 10.1186/s13063-024-08133-6
doi:
Substances chimiques
Antitubercular Agents
0
Isoniazid
V83O1VOZ8L
Rifampin
VJT6J7R4TR
Pyrazinamide
2KNI5N06TI
Aspirin
R16CO5Y76E
Banques de données
ClinicalTrials.gov
['NCT05917340']
Types de publication
Journal Article
Clinical Trial Protocol
Langues
eng
Sous-ensembles de citation
IM
Pagination
294Subventions
Organisme : Indian Council of Medical Research
ID : IIRP-2023-0000202
Informations de copyright
© 2024. The Author(s).
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