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Tuberculous MeningitisPhase 2AspirinTBMNCT02237365

A Pilot Study of Adjunctive Aspirin for the Treatment of HIV Negative Adults With Tuberculous Meningitis

A Phase 2 study testing 81mg aspirin and 1000mg aspirin in people with Tuberculous Meningitis, run by Oxford University Clinical Research Unit, Vietnam at 1 site in Vietnam.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Tuberculous meningitis is a severe brain infection which often causes disability and death even when treated with the best available treatment. Aspirin is a type of anti-inflammation drug which can reduce the inflammatory response in brains of patients with tuberculous meningitis, and therefore may decrease some of… 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?
81mg aspirin and 1000mg aspirin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
120 participants
Where
1 siteVietnam
Study dates
17 Oct 2014to 22 Dec 2016
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Male or female, aged 18 years or above.
  • Suspected TBM and anti-tuberculosis chemotherapy either planned or started
  • Less than 3 days of anti-tuberculosis chemotherapy taken for the current infection
  • Patient or representative (if the patient is unable) is willing and able to give informed consent for participation in the study.

Who cannot join

  • HIV infection (negative rapid test or Elisa test is required)
  • Unlikely, for any reason, to be able to have an MRI brain scan within 5 days (120 hours) of randomisation
  • Known or suspected infection with multi-drug resistant tuberculosis (resistant to at least isoniazid and rifampicin)
  • Unable to take isoniazid, rifampicin, or pyrazinamide at recommended doses for any reason
  • History of diagnosed peptic ulceration or gastro-intestinal bleeding
  • Active gastro-intestinal bleeding is suspected
Show all 12Show fewer
  • Taken >1 dose of aspirin (at any dose) or any other non-steroidal anti-inflammatory drugs for any reason within 2 weeks of screening
  • Aspirin considered mandatory for any reason by the attending physician
  • Aspirin considered to be contraindicated for any reason by the attending physician
  • Pregnancy or breast feeding (negative urine pregnancy test for all females of child-bearing age)
  • Dexamethasone considered to be contraindicated for any reason by the attending physician
  • Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.

Trial locations and contacts

1 site in 1 country.

Vietnam1 site

  • Hospital for Tropical Diseases

    Ho Chi Minh City

Other trials in Vietnam

About this study

Official title: A Pilot Phase II Randomized Controlled Double Blind Trial of 81mg Aspirin Daily vs. 1000 mg Aspirin Daily vs. Placebo as Adjunctive Therapy in HIV Negative Adults With Tuberculous Meningitis

Tuberculous meningitis is a severe brain infection which often causes disability and death even when treated with the best available treatment. Aspirin is a type of anti-inflammation drug which can reduce the inflammatory response in brains of patients with tuberculous meningitis, and therefore may decrease some of the most severe outcomes. This study compares the use of aspirin (at 2 different doses) versus placebo as an additional therapy to the standard treatment to see if aspirin is safe and helpful in reducing disability and death from tuberculous meningitis. Patients will be treated with aspirin or placebo for 60 days and followed up while on standard treatment for 8 months.

Read the detailed description

The study is a parallel group, double blind, randomised, placebo controlled trial of 60 days treatment with placebo vs. 81mg daily dose vs. 1000mg daily dose aspirin for the treatment of HIV-uninfected adults with tuberculous meningitis.

All patients will receive standard anti-tuberculous chemotherapy and adjunctive dexamethasone, according to Viet Nam National Tuberculosis Programme guidelines. Participants will be stratified by Medical Research Council UK disease severity grade, and randomized at enrollment to one of three study arms (1:1:1 ratio). Patients will be admitted to hospital for at least the first 14 days of study treatment enabling real-time active surveillance of any adverse events after which they will be discharged according to clinical care with continued monitoring.

A schedule of clinical and laboratory monitoring including lumbar puncture, pharmacokinetic assessment of peripheral blood monocyte/macrophage antimicrobial activity, clinical assessments, brain magnetic resonance imaging (MRI) and neurological assessment will manage patient safety and capture study outcomes.

Being tested
81mg aspirin, 1000mg aspirin, Placebo
Keywords
neurological disability, tuberculous meningitis (TBM), safety, aspirin, efficacy
Medical subject headings
Tuberculosis, Meningeal

What participants receive

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

  • 81mg aspirinDrug

    1 tablet of 81mg aspirin and 2 tablets of placebo (visually matched to 500mg aspirin) daily for 60 days

  • 1000mg aspirinDrug

    1 tablet of 81mg placebo (visually matched to 81mg aspirin) and 2 tablets of 500mg aspirin daily for 60 days

  • PlaceboDrug

    1 tablet of 81mg placebo (visually matched to 81mg aspirin) and 2 tablets of 500mg placebo (visually matched to 500mg aspirin) daily for 60 days

Study groups in NCT02237365
Study groupRoleWhat they receive
81mg aspirinExperimentalAspirin 81mg daily for 60 days
Receives: Drug: 81mg aspirin
1000mg aspirinExperimentalAspirin 1000mg daily for 60 days
Receives: Drug: 1000mg aspirin
PlaceboPlacebo comparatorVisually matched placebo daily for 60 days
Receives: Drug: Placebo

What is being measured

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

  1. Number of episodes of either cerebral bleeding or clinically significant upper-gastro-intestinal bleeding (composite endpoint)

    Primary Safety Endpoint: Number of episodes of:

    1. Cerebral bleeding confirmed by brain imaging and/or
    2. Clinically significant upper-gastro-intestinal bleeding, defined as: a) Vomiting fresh or changed blood of any volume; b) Melena; c) Unexplained drop in haemoglobin concentration of >2g/L or; d) Greater than 5mls of fresh or changed blood aspirated from nasogastric tube

    Measured: 60 days

  2. Number of episodes of MRI-proven brain infarction or death (composite endpoint)

    Primary Efficacy Endpoint: Number of episodes of

    1. MRI-proven brain infarction and/or
    2. Death

    Measured: 60 days

Secondary outcomes (8)

  1. Time to death

    Measured: 240 days

  2. Number of grade 3&4 and serious adverse events

    Graded according to Common Terminology Criteria for Adverse Events (CTCAE) definitions

    Measured: 60 days

  3. Duration of hospital stay

    Number of days admitted to hospital during the study period

    Measured: 240 days

  4. Neurological disability score

    Assessed by the modified Rankin score and Glasgow outcome score

    Measured: 60 days

  5. Neurological disability score

    Assessed by the modified Rankin score and Glasgow outcome score

    Measured: 240 days

  6. Resolution of cerebrospinal fluid (CSF) inflammation

    Evaluated by measurement of CSF leucocytes, protein, glucose, cytokines (TNF-α, IL-1β, IL-8, IL-10, IFNγ) and eicosanoids (15-epi-Lipoxin, Lipoxin A4, LTB4, PGE2, TBXB2, PGD2)

    Measured: 30 days

  7. Antimicrobial activity of peripheral blood monocyte/macrophages

    Difference between measured antimicrobial activity at baseline and 240 days

    Measured: 240 days

  8. Proportion of patients with MRI-proven brain infarction

    Measured: 240 days

Timeline

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

  1. First posted11 Sep 2014 (estimated)
  2. Study start17 Oct 2014
  3. Primary completion24 Jun 2016
  4. Study completion22 Dec 2016

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02237365
Sponsor's protocol ID
23TB
Acronym
AspirinTBM
Status last verified
Mar 2017
First submitted
9 Sep 2014
Last updated
7 Mar 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Mai NTH, Dobbs N, Phu NH, Colas RA, Thao LTP, Thuong NTT, Nghia HDT, Hanh NHH, Hang NT, Heemskerk AD, Day JN, Ly L, Thu DDA, Merson L, Kestelyn E, Wolbers M, Geskus R, Summers D, Chau NVV, Dalli J, Thwaites GE. A randomised double blind placebo controlled phase 2 trial of adjunctive aspirin for tuberculous meningitis in HIV-uninfected adults. Elife. 2018 Feb 27;7:e33478. doi: 10.7554/eLife.33478.

    PubMed 29482717

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 81mg aspirin and 1000mg aspirin in people with Tuberculous Meningitis, run by Oxford University Clinical Research Unit, Vietnam at 1 site in Vietnam.

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 4 inclusion and 12 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: finished, as of the sponsor's last update on 7 Mar 2017. 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 Vietnam. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of episodes of either cerebral bleeding or clinically significant upper-gastro-intestinal bleeding (composite endpoint) (time frame: 60 days). The study lists 2 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 NCT02237365, 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 7 Mar 2017.

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