Intensified Short Course Regimen for TBM in Adults (INSHORT)

December 20, 2023 updated by: Leeberk Raja Inbaraj, Indian Council of Medical Research

Comparative Evaluation of Intensified Short Course Regimen and Standard Regimen for Adults TB Meningitis : an Open-label Randomized Controlled Trial

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
372

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • India
    • Tamil Nadu
      • Chennai, Tamil Nadu, India, 600031
        • ICMR- National Institute for Research in Tuberculosis
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm- 1( Intervention arm with aspirin)
Intensified with high dose rifampicin, moxifloxacin, aspirin and steroids in the initial two months.
Drug: High dose rifampicin (25mg/kg)
Given for 2 months
Drug: Moxifloxacin 400mg
Given for 2 months
Drug: Aspirin 150 mg
Given for 2 months
Drug: Isoniazid
Given for 6 months
Drug: Pyrazinamide
Given for 6 months
Drug: Steroid
Tapering dose of dexamethasone or prednisolone upto 8 weeks
Drug: Rifampicin
Standard dose for 4 months after the initial treatment with high dose
Experimental: Arm -2 (Intervention arm without aspirin)
Intensified with high dose rifampicin, moxifloxacin and steroids in the initial two months.
Drug: High dose rifampicin (25mg/kg)
Given for 2 months
Drug: Moxifloxacin 400mg
Given for 2 months
Drug: Isoniazid
Given for 6 months
Drug: Pyrazinamide
Given for 6 months
Drug: Steroid
Tapering dose of dexamethasone or prednisolone upto 8 weeks
Drug: Rifampicin
Standard dose for 4 months after the initial treatment with high dose
Active Comparator: Arm -3 (Control)
Regimen as per the current National Tuberculosis Elimination Program in India.
Drug: HRZE
2 months
Drug: HRE
7-10 months as per TB program guidelines

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mortality rate
Time Frame: 12 months
12 months
Mortality rate
Time Frame: 12 months
Between two groups
12 months
Disability rate
Time Frame: 12 months
Measured by Modified Rankin scale. A score of 0 to 2 will be considered as no disability and 3-5 will be considered as disability. 0 - no symptoms ; 5 - severe disability
12 months
Disability rate
Time Frame: 24 months
Measured by Modified Rankin scale. A score of 0 to 2 will be considered as no disability and 3-5 will be considered as disability. 0 - no symptoms ; 5 - severe disability
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum Plasma Concentration [Cmax] of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)
Time Frame: Between week 1 & 2
Plasma Cmax, cerebrospinal fluid [CSF] Cmax, and plasma/CSF Cmax ratio
Between week 1 & 2
Time for maximal concentration of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)
Time Frame: Between week 1 & 2
Plasma Tmax, cerebrospinal fluid [CSF] Tmax, and plasma/CSF Tmax ratio
Between week 1 & 2
Area Under the Curve (AUC) of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)
Time Frame: Between week 1 & 2
Plasma Tmax, cerebrospinal fluid [CSF] Tmax, and plasma/CSF Tmax ratio
Between week 1 & 2
Grade 3 & 4 adverse events
Time Frame: 12 months
Comparison of the number of participants who develop Grade 3 or Grade 4 adverse events (according to Division of AIDS (DAIDS) criteria) during treatment. Grade 1 - mild event ; Grade 2 - moderate event; Grade 3- severe event ;Grade 4 - potentially life-threatening
12 months
Grade 3 & 4 adverse events
Time Frame: 24 months
Comparison of the number of participants who develop Grade 3 or Grade 4 adverse events (according to Division of AIDS (DAIDS) criteria) during treatment. Grade 1 - mild event ; Grade 2 - moderate event; Grade 3- severe event ;Grade 4 - potentially life-threatening
24 months
Quality of life (QoL) in both the arms and change in QoL during the follow up
Time Frame: 6,12 & 24 months
Using WHO Short form -36 (SF-36), a questionnaire to assess health related outcomes
6,12 & 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Indian Council of Medical Research

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Christian Medical College, Vellore, India
Jawaharlal Institute of Postgraduate Medical Education & Research
Madras Medical College
Rural Development Trust Hospital
North Eastern Indira Gandhi Regional Institute of Health ans Medical Sciences
All India Institute of Medical Sciences, Jodhpur

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 8, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 15, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 23, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 21, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 20, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NIRT-IEC No:2023 003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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