Intensified Short Course Regimen for TBM in Adults

NCT ID: NCT05917340

Last Updated: 2023-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

372 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-31

Study Completion Date

2027-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Tuberculous meningitis (TBM) is the most lethal form of extra pulmonary tuberculosis. This devastating disease kills almost a third of its sufferers and disables a significant proportion of the survivors. TBM poses one of the most difficult diagnostic and therapeutic challenges in modern clinical practice. High-quality robust clinical trials have made a considerable contribution to the treatment of pulmonary tuberculosis in the last four decades. However, evidence from such clinical trials is lacking in TBM and the treatment remains uncertain. There is a significant variation in the choice, dose and duration of drugs between countries, institutions and clinicians. Investigators propose a multi-centric open-label clinical trial to assess the efficacy of short-course anti-TB drugs with high dose rifampicin, and moxifloxacin along with conventional anti-TB drugs and adjuvant therapy with aspirin and corticosteroids. Controls will receive standard treatment as per national guidelines for TBM. The investigators also aim to assess the safety and tolerability of high-dose Rifampicin and Moxifloxacin and the Pharmacodynamics and Pharmacokinetics parameters of ATT (Rifampicin, INH, Moxifloxacin and Pyrazinamide) in CSF between the two groups

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Tuberculous Meningitis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm- 1( Intervention arm with aspirin)

Intensified with high dose rifampicin, moxifloxacin, aspirin and steroids in the initial two months.

Group Type EXPERIMENTAL

High dose rifampicin (25mg/kg)

Intervention Type DRUG

Given for 2 months

Moxifloxacin 400mg

Intervention Type DRUG

Given for 2 months

Aspirin 150 mg

Intervention Type DRUG

Given for 2 months

Isoniazid

Intervention Type DRUG

Given for 6 months

Pyrazinamide

Intervention Type DRUG

Given for 6 months

Steroid

Intervention Type DRUG

Tapering dose of dexamethasone or prednisolone upto 8 weeks

Rifampicin

Intervention Type DRUG

Standard dose for 4 months after the initial treatment with high dose

Arm -2 (Intervention arm without aspirin)

Intensified with high dose rifampicin, moxifloxacin and steroids in the initial two months.

Group Type EXPERIMENTAL

High dose rifampicin (25mg/kg)

Intervention Type DRUG

Given for 2 months

Moxifloxacin 400mg

Intervention Type DRUG

Given for 2 months

Isoniazid

Intervention Type DRUG

Given for 6 months

Pyrazinamide

Intervention Type DRUG

Given for 6 months

Steroid

Intervention Type DRUG

Tapering dose of dexamethasone or prednisolone upto 8 weeks

Rifampicin

Intervention Type DRUG

Standard dose for 4 months after the initial treatment with high dose

Arm -3 (Control)

Regimen as per the current National Tuberculosis Elimination Program in India.

Group Type ACTIVE_COMPARATOR

HRZE

Intervention Type DRUG

2 months

HRE

Intervention Type DRUG

7-10 months as per TB program guidelines

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

High dose rifampicin (25mg/kg)

Given for 2 months

Intervention Type DRUG

Moxifloxacin 400mg

Given for 2 months

Intervention Type DRUG

Aspirin 150 mg

Given for 2 months

Intervention Type DRUG

Isoniazid

Given for 6 months

Intervention Type DRUG

Pyrazinamide

Given for 6 months

Intervention Type DRUG

Steroid

Tapering dose of dexamethasone or prednisolone upto 8 weeks

Intervention Type DRUG

Rifampicin

Standard dose for 4 months after the initial treatment with high dose

Intervention Type DRUG

HRZE

2 months

Intervention Type DRUG

HRE

7-10 months as per TB program guidelines

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

A patient will be eligible for entry to the trial if ALL of the following conditions are satisfied

1. Adults (\> 18 years) with or without HIV infection
2. Possible, probable or definite TBM according to Lancet consensus diagnostic criteria
3. Willing to give written informed consent
4. Is willing to have an HIV test.
5. Residing within 100 km of the study sites
6. Express willingness to attend the treatment centre for supervised treatment
7. Express willingness to adhere to the trial procedures and follow-up schedule.
8. Agrees to use effective barrier contraception during the period of the treatment in case of female participants

Exclusion Criteria

Patients will not be eligible for the trial if they meet ANY of the following criteria

1. Known current/previous drug resistance to ATT (Rifampicin, INH, FQ)\*\*
2. Concurrent or known diagnosis any other meningitis such as bacterial, viral, and fungal.
3. Currently having an uncontrolled cardiac arrhythmia or ECG abnormalities which are contradiction for the administration of moxifloxacin including prolonged QTc. QTc value define as \>450 ms in males and \>460 ms in females measured in lead II or V5 on a standard 12-lead ECG.
4. Has clinical icterus or hepatic impairment characterized by serum bilirubin level above the normal laboratory reference range with abnormal liver enzymes, or isolated alanine aminotransferase (ALT) and/ or aspartate aminotransferase (AST) levels above 5 times the upper limit of the normal laboratory reference range
5. Previous history of anti-TB treatment, If any, should not exceed one month in the past and not more than 7 days in the preceding one month.
6. pregnant or lactating women
7. rapid clinical deterioration or very sick and moribund during the screening process, renal failure, liver disease or any condition (social or medical) that in the opinion of the investigator would make trial participation unreliable or unsafe.
8. Has a known allergy to any of the drugs proposed to be used in the trial regimen

* All participants with Rifampicin resistance will be excluded at baseline from the study. Participants with H, FQ and Z resistance identified from MGIT results done at baseline will be referred back to NTEP for appropriate management and their numbers will be compensated.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

All India Institute of Medical Sciences, Jodhpur

OTHER_GOV

Sponsor Role collaborator

Christian Medical College, Vellore, India

OTHER

Sponsor Role collaborator

Jawaharlal Institute of Postgraduate Medical Education & Research

OTHER_GOV

Sponsor Role collaborator

North Eastern Indira Gandhi Regional Institute of Health ans Medical Sciences

OTHER_GOV

Sponsor Role collaborator

Madras Medical College

OTHER_GOV

Sponsor Role collaborator

Rural Development Trust Hospital

OTHER

Sponsor Role collaborator

Indian Council of Medical Research

OTHER_GOV

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Leeberk Raja Inbaraj

Scientist-E (Medical)

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

ICMR- National Institute for Research in Tuberculosis

Chennai, Tamil Nadu, India

Site Status

Countries

Review the countries where the study has at least one active or historical site.

India

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Dr Leeberk Raja Inbaraj, MBBS MD

Role: CONTACT

044-28369527

Dr Bella Devaleenal, MBBS MPH

Role: CONTACT

044-28369538

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Dr Padmapriyadarsini Chandrasekaran, MBBS DNB MS PhD

Role: primary

044-28369500

References

Explore related publications, articles, or registry entries linked to this study.

Inbaraj LR, Manesh A, Ponnuraja C, Bhaskar A, Srinivasalu VA, Daniel BD. 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). Trials. 2024 May 2;25(1):294. doi: 10.1186/s13063-024-08133-6.

Reference Type DERIVED
PMID: 38693583 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NIRT-IEC No:2023 003

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.