NCT02237365

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Oct 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 9, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 11, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

October 17, 2014

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 24, 2016

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 22, 2016

Completed
Last Updated

March 7, 2017

Status Verified

March 1, 2017

Enrollment Period

1.7 years

First QC Date

September 9, 2014

Last Update Submit

March 5, 2017

Conditions

Tuberculous Meningitis

Keywords

neurological disabilitytuberculous meningitis (TBM)safetyaspirinefficacy

Outcome Measures

Primary Outcomes (2)

  • 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

    60 days

  • 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

    60 days

Secondary Outcomes (8)

  • Time to death

    240 days

  • Number of grade 3&4 and serious adverse events

    60 days

  • Duration of hospital stay

    240 days

  • Neurological disability score

    60 days

  • Neurological disability score

    240 days

  • +3 more secondary outcomes

Study Arms (3)

81mg aspirin

EXPERIMENTAL

Aspirin 81mg daily for 60 days

Drug: 81mg aspirin

1000mg aspirin

EXPERIMENTAL

Aspirin 1000mg daily for 60 days

Drug: 1000mg aspirin

Placebo

PLACEBO COMPARATOR

Visually matched placebo daily for 60 days

Drug: Placebo

Interventions

81mg aspirinDRUG

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

81mg aspirin
1000mg aspirinDRUG

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

1000mg aspirin
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

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital for Tropical Diseases

Ho Chi Minh City, Vietnam

Location

Related Publications (1)

  • 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.

    PMID: 29482717DERIVED

Related Links

MeSH Terms

Conditions

Tuberculosis, Meningeal

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Meningitis, BacterialCentral Nervous System Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsTuberculosis, Central Nervous SystemTuberculosis, ExtrapulmonaryTuberculosisMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsCentral Nervous System InfectionsCentral Nervous System DiseasesNervous System DiseasesMeningitisNeuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

SalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Study Officials

  • Guy Thwaites, MD, PhD

    Oxford University of Clinical Research

    PRINCIPAL INVESTIGATOR

  • Nguyen H Phu, MD, PhD

    Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 9, 2014

First Posted

September 11, 2014

Study Start

October 17, 2014

Primary Completion

June 24, 2016

Study Completion

December 22, 2016

Last Updated

March 7, 2017

Record last verified: 2017-03

Locations

VN(1)