search
Back to results

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

Primary Purpose

Tuberculous Meningitis

Status
Completed
Phase
Phase 2
Locations
Vietnam
Study Type
Interventional
Intervention
81mg aspirin
1000mg aspirin
Placebo
Sponsored by
Oxford University Clinical Research Unit, Vietnam
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculous Meningitis focused on measuring neurological disability, tuberculous meningitis (TBM), safety, aspirin, efficacy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital for Tropical Diseases

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

81mg aspirin

1000mg aspirin

Placebo

Arm Description

Aspirin 81mg daily for 60 days

Aspirin 1000mg daily for 60 days

Visually matched placebo daily for 60 days

Outcomes

Primary Outcome Measures

Number of episodes of either cerebral bleeding or clinically significant upper-gastro-intestinal bleeding (composite endpoint)
Primary Safety Endpoint: Number of episodes of: Cerebral bleeding confirmed by brain imaging and/or 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
Number of episodes of MRI-proven brain infarction or death (composite endpoint)
Primary Efficacy Endpoint: Number of episodes of MRI-proven brain infarction and/or Death

Secondary Outcome Measures

Time to death
Number of grade 3&4 and serious adverse events
Graded according to Common Terminology Criteria for Adverse Events (CTCAE) definitions
Duration of hospital stay
Number of days admitted to hospital during the study period
Neurological disability score
Assessed by the modified Rankin score and Glasgow outcome score
Neurological disability score
Assessed by the modified Rankin score and Glasgow outcome score
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)
Antimicrobial activity of peripheral blood monocyte/macrophages
Difference between measured antimicrobial activity at baseline and 240 days
Proportion of patients with MRI-proven brain infarction

Full Information

First Posted
September 9, 2014
Last Updated
March 5, 2017
Sponsor
Oxford University Clinical Research Unit, Vietnam
Collaborators
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
search

1. Study Identification

Unique Protocol Identification Number
NCT02237365
Brief Title
A Pilot Study of Adjunctive Aspirin for the Treatment of HIV Negative Adults With Tuberculous Meningitis
Acronym
AspirinTBM
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
October 17, 2014 (Actual)
Primary Completion Date
June 24, 2016 (Actual)
Study Completion Date
December 22, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oxford University Clinical Research Unit, Vietnam
Collaborators
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculous Meningitis
Keywords
neurological disability, tuberculous meningitis (TBM), safety, aspirin, efficacy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Actual)

8. Arms, Groups, and Interventions

Arm Title
81mg aspirin
Arm Type
Experimental
Arm Description
Aspirin 81mg daily for 60 days
Arm Title
1000mg aspirin
Arm Type
Experimental
Arm Description
Aspirin 1000mg daily for 60 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Visually matched placebo daily for 60 days
Intervention Type
Drug
Intervention Name(s)
81mg aspirin
Intervention Description
1 tablet of 81mg aspirin and 2 tablets of placebo (visually matched to 500mg aspirin) daily for 60 days
Intervention Type
Drug
Intervention Name(s)
1000mg aspirin
Intervention Description
1 tablet of 81mg placebo (visually matched to 81mg aspirin) and 2 tablets of 500mg aspirin daily for 60 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Number of episodes of either cerebral bleeding or clinically significant upper-gastro-intestinal bleeding (composite endpoint)
Description
Primary Safety Endpoint: Number of episodes of: Cerebral bleeding confirmed by brain imaging and/or 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
Time Frame
60 days
Title
Number of episodes of MRI-proven brain infarction or death (composite endpoint)
Description
Primary Efficacy Endpoint: Number of episodes of MRI-proven brain infarction and/or Death
Time Frame
60 days
Secondary Outcome Measure Information:
Title
Time to death
Time Frame
240 days
Title
Number of grade 3&4 and serious adverse events
Description
Graded according to Common Terminology Criteria for Adverse Events (CTCAE) definitions
Time Frame
60 days
Title
Duration of hospital stay
Description
Number of days admitted to hospital during the study period
Time Frame
240 days
Title
Neurological disability score
Description
Assessed by the modified Rankin score and Glasgow outcome score
Time Frame
60 days
Title
Neurological disability score
Description
Assessed by the modified Rankin score and Glasgow outcome score
Time Frame
240 days
Title
Resolution of cerebrospinal fluid (CSF) inflammation
Description
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)
Time Frame
30 days
Title
Antimicrobial activity of peripheral blood monocyte/macrophages
Description
Difference between measured antimicrobial activity at baseline and 240 days
Time Frame
240 days
Title
Proportion of patients with MRI-proven brain infarction
Time Frame
240 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guy Thwaites, MD, PhD
Organizational Affiliation
Oxford University of Clinical Research
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nguyen H Phu, MD, PhD
Organizational Affiliation
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital for Tropical Diseases
City
Ho Chi Minh City
Country
Vietnam

12. IPD Sharing Statement

Citations:
PubMed Identifier
29482717
Citation
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. Erratum In: Elife. 2023 Mar 21;12:
Results Reference
derived
Links:
URL
http://www.oucru.org
Description
Oxford University Clinical Research Unit, Viet Nam

Learn more about this trial

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

We'll reach out to this number within 24 hrs