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

Brief Title

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

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

Brief 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 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.
    

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 Time to death

Condition

Tuberculous Meningitis

Intervention

81mg aspirin

Study Arms / Comparison Groups

 81mg aspirin
Description:  Aspirin 81mg daily for 60 days

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

120

Start Date

October 17, 2014

Completion Date

December 22, 2016

Primary Completion Date

June 24, 2016

Eligibility Criteria

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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

          -  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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Guy Thwaites, MD, PhD, , 

Location Countries

Vietnam

Location Countries

Vietnam

Administrative Informations


NCT ID

NCT02237365

Organization ID

23TB


Responsible Party

Sponsor

Study Sponsor

Oxford University Clinical Research Unit, Vietnam

Collaborators

 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Study Sponsor

Guy Thwaites, MD, PhD, Principal Investigator, Oxford University of Clinical Research


Verification Date

March 2017