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Tuberculous MeningitisPhase 3INSHORTNCT05917340

Intensified Short Course Regimen for TBM in Adults

A Phase 3 study testing High dose rifampicin (25mg/kg), Moxifloxacin 400mg and Aspirin 150 mg in people with Tuberculous Meningitis, run by Indian Council of Medical Research at 1 site in India.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Tuberculous Meningitis
What is being tested?
High dose rifampicin (25mg/kg), Moxifloxacin 400mg and Aspirin 150 mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
372 participants
Where
1 siteIndia
Study dates
Mar 2024to Sep 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A patient will be eligible for entry to the trial if ALL of the following conditions are satisfied
  • Adults (> 18 years) with or without HIV infection
  • Possible, probable or definite TBM according to Lancet consensus diagnostic criteria
  • Willing to give written informed consent
  • Is willing to have an HIV test.
  • Residing within 100 km of the study sites
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  • Express willingness to attend the treatment centre for supervised treatment
  • Express willingness to adhere to the trial procedures and follow-up schedule.
  • Agrees to use effective barrier contraception during the period of the treatment in case of female participants

Who cannot join

  • Patients will not be eligible for the trial if they meet ANY of the following criteria
  • Known current/previous drug resistance to ATT (Rifampicin, INH, FQ)**
  • Concurrent or known diagnosis any other meningitis such as bacterial, viral, and fungal.
  • 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.
  • 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
  • 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.
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  • pregnant or lactating women
  • 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.
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Dr Leeberk Raja Inbaraj, MBBS MD contact

044-28369527

leeberk.raja@icmr.gov.in

Dr Bella Devaleenal, MBBS MPH contact

044-28369538

belladevalleenal.d@icmr.gov.in

India1 site

  • ICMR- National Institute for Research in Tuberculosis

    Chennai, Tamil Nadu, 600031

    Dr Padmapriyadarsini Chandrasekaran, MBBS DNB MS PhD, 044-28369500, nirtdirector@icmr.gov.in

Other trials in India

About this study

Official title: 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

Being tested
High dose rifampicin (25mg/kg), Moxifloxacin 400mg, Aspirin 150 mg, Isoniazid, Pyrazinamide
Medical subject headings
Tuberculosis, Meningeal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • High dose rifampicin (25mg/kg)Drug

    Given for 2 months

  • Moxifloxacin 400mgDrug

    Given for 2 months

  • Aspirin 150 mgDrug

    Given for 2 months

  • IsoniazidDrug

    Given for 6 months

  • PyrazinamideDrug

    Given for 6 months

  • SteroidDrug

    Tapering dose of dexamethasone or prednisolone upto 8 weeks

  • RifampicinDrug

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

  • HRZEDrug

    2 months

  • HREDrug

    7-10 months as per TB program guidelines

Study groups in NCT05917340
Study groupRoleWhat they receive
Arm- 1( Intervention arm with aspirin)ExperimentalIntensified with high dose rifampicin, moxifloxacin, aspirin and steroids in the initial two months.
Receives: Drug: High dose rifampicin (25mg/kg); Drug: Moxifloxacin 400mg; Drug: Aspirin 150 mg; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Steroid; Drug: Rifampicin
Arm -2 (Intervention arm without aspirin)ExperimentalIntensified with high dose rifampicin, moxifloxacin and steroids in the initial two months.
Receives: Drug: High dose rifampicin (25mg/kg); Drug: Moxifloxacin 400mg; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Steroid; Drug: Rifampicin
Arm -3 (Control)Active comparatorRegimen as per the current National Tuberculosis Elimination Program in India.
Receives: Drug: HRZE; Drug: HRE

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mortality rate

    Between two groups

    Measured: 12 months

  2. Disability rate

    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

    Measured: 12 months

  3. Mortality rate

    Measured: 12 months

  4. Disability rate

    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

    Measured: 24 months

Secondary outcomes (6)

  1. Maximum Plasma Concentration [Cmax] of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)

    Plasma Cmax, cerebrospinal fluid [CSF] Cmax, and plasma/CSF Cmax ratio

    Measured: Between week 1 & 2

  2. Time for maximal concentration of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)

    Plasma Tmax, cerebrospinal fluid [CSF] Tmax, and plasma/CSF Tmax ratio

    Measured: Between week 1 & 2

  3. Area Under the Curve (AUC) of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)

    Plasma Tmax, cerebrospinal fluid [CSF] Tmax, and plasma/CSF Tmax ratio

    Measured: Between week 1 & 2

  4. Grade 3 & 4 adverse events

    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

    Measured: 12 months

  5. Grade 3 & 4 adverse events

    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

    Measured: 24 months

  6. Quality of life (QoL) in both the arms and change in QoL during the follow up

    Using WHO Short form -36 (SF-36), a questionnaire to assess health related outcomes

    Measured: 6,12 & 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2023
  2. Study startMar 2024 (estimated)
  3. Primary completionSep 2027 (estimated)
  4. Study completionSep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
372 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05917340
Sponsor's protocol ID
NIRT-IEC No:2023 003
Acronym
INSHORT
Status last verified
Dec 2023
First submitted
8 Jun 2023
Last updated
21 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38693583

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing High dose rifampicin (25mg/kg), Moxifloxacin 400mg and Aspirin 150 mg in people with Tuberculous Meningitis, run by Indian Council of Medical Research at 1 site in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Dr Leeberk Raja Inbaraj, MBBS MD (044-28369527, leeberk.raja@icmr.gov.in), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mortality rate (time frame: 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05917340, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2023.

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