Adjunctive Acetylsalicylic Acid and Ibuprofen for Tuberculosis

NCT ID: NCT04575519

Last Updated: 2024-03-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

354 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-04

Study Completion Date

2025-06-30

Brief Summary

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The purpose of this study is to assess the efficacy and safety of 2 repurposed drugs (acetylsalicylic acid and ibuprofen), for use as adjunct therapy added to, and compared with, the standard of care (SoC) WHO-recommended TB regimen in drug-sensitive (DS) and multi-drug resistant (MDR) TB patients.

Detailed Description

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If eligible and informed consent obtained, patients will be randomized 1:1:1 into one of the following 3 arms, to receive:

1. Standard of Care (SoC) TB treatment + placebo twice daily during the first 4 weeks of TB treatment followed by placebo once daily for an additional 4 weeks. (control group).
2. SoC TB treatment + acetylsalicylic acid 300mg twice daily during the first 4 weeks of TB treatment followed by acetylsalicylic acid 300mg once daily for an additional 4 weeks.
3. SoC TB treatment + ibuprofen 400mg twice daily during the first 4 weeks of TB treatment followed by ibuprofen 400mg once daily for an additional 4 weeks.

Conditions

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Tuberculosis, Pulmonary Tuberculosis, MDR Tuberculosis Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multicentre, phase IIB, placebo controlled, randomized, 3-arm trial in DS and MDR TB patient
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Control group

Standard of Care (SoC) TB treatment + placebo twice daily during first 4 weeks of TB treatment followed by placebo once daily for an additional 4 weeks.

Group Type ACTIVE_COMPARATOR

Control group

Intervention Type DRUG

placebo 2 months treatment: 2 tablets during 4 weeks + 1 tablet during 4 weeks

SoC TB

Intervention Type DRUG

Standard of Care Tuberculosis treatment

SoC TB + ASA group

Standard of Care (SoC) TB treatment + acetylsalicylic acid 300mg twice daily during first 4 weeks of TB treatment followed by aspirin 300mg once daily for an additional 4 weeks.

Group Type EXPERIMENTAL

ASA group

Intervention Type DRUG

Acetylsalicylic acid 2 months treatment: 2 tablets during 4 weeks (600 mg daily) + 1 tablet during 4 weeks (300 mg daily)

SoC TB

Intervention Type DRUG

Standard of Care Tuberculosis treatment

SoC TB + IBU group

Standard of Care (SoC) TB treatment + ibuprofen 400mg twice daily during first 4 weeks of TB treatment followed by ibuprofen 400mg once daily for an additional 4 weeks

Group Type EXPERIMENTAL

IBU group

Intervention Type DRUG

Ibuprofen 2 months treatment: 2 tablets during 4 weeks (800 mg daily) + 1 tablet during 4 weeks (400 mg daily)

SoC TB

Intervention Type DRUG

Standard of Care Tuberculosis treatment

Interventions

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Control group

placebo 2 months treatment: 2 tablets during 4 weeks + 1 tablet during 4 weeks

Intervention Type DRUG

ASA group

Acetylsalicylic acid 2 months treatment: 2 tablets during 4 weeks (600 mg daily) + 1 tablet during 4 weeks (300 mg daily)

Intervention Type DRUG

IBU group

Ibuprofen 2 months treatment: 2 tablets during 4 weeks (800 mg daily) + 1 tablet during 4 weeks (400 mg daily)

Intervention Type DRUG

SoC TB

Standard of Care Tuberculosis treatment

Intervention Type DRUG

Other Intervention Names

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placebo Acetylsalicylic acid (ASA) Ibuprofen (IBU) Standard of Care Tuberculosis treatment

Eligibility Criteria

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Inclusion Criteria

1. Adults, 18- 60 years of age
2. Written informed consent in a language they understand. This includes informed consent to be in the trial and informed consent to collect specimens.
4. Women of childbearing potential (including females \<2 years post-menopausal) must have a negative pregnancy test at enrolment.
5. Participants must be willing to have an HIV test done unless there is compelling evidence that the patient is HIV-infected at the time of randomization.

Exclusion Criteria

1. Has a comorbid condition where treatment with aspirin, ibuprofen or other NSAID is indicated (e.g. cardiovascular disease, rheumatic fever, chronic pain, etc.)
2. People institutionalized (incarceration in jail or prison, or due to chronic mental illness). If incarcerated during the study, participants may be terminated, those incarcerated in the first 8 weeks of follow up will be late exclusions and replaced\*. Patients either who are planned to be hospitalized or currently hospitalized whilst treated for MDR TB in a TB hospital or ward may be enrolled.
3. Receipt of multi-drug TB treatment (including rifamycin plus isoniazid preventive treatment regimens) for ≥3 days in the 6 months prior to randomization. Participants who have received ≥3 days of TB preventive treatment in the month prior to TB treatment initiation will also be excluded.
4. Currently Pregnancy/breastfeeding. Women who conceive and are found to be pregnant in the first 4 weeks of the trial will be terminated from the trial and excluded from the analysis.
5. Any of the following laboratory parameters taken prior to randomization:

* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 x upper limit of normal (ULN);
* Total bilirubin \> 2 x ULN;
* Neutrophil count ≤ 700 neutrophils /mm3;
* Platelet count \< 50,000 cells / mm3
* Haemoglobin concentration less than 8 g/dL
* Serum creatinine concentration more than twice the upper limit of normal
6. Co-treatment in the three months prior to randomization, or planned treatment over the course of the trial follow up with any one of the following agents:

* anticoagulant therapy
* immune modulating therapy (cancer treatments, any oral or daily use of inhaled steroids;
* Antacids or proton pump inhibitors - including self-treatment and prescription
7. History or clinical record of sensitivity, asthma or allergy that could be attributed to NSAIDs
8. Weight \< 45kg at baseline.
9. History or clinical record suggestive of any of the following in the past two years:

* peptic ulcer disease or gastro-intestinal bleeding,
* coagulopathy or other bleeding disorder,
* renal disease requiring hospitalization - in addition, any prior record at any time of acute kidney injury will be an exclusion criterion.
* liver disease requiring further investigation or hospitalization,
* underlying cardiovascular disease or risk factors for cardiovascular disease.
10. Patients with HIV infection (irrespective of ART status) if:

* CD4 \<350 cells/mm3
* if on ART, unsuppressed (\>200 copies/ml) viral load
* if not on ART, either in the opinion of the attending doctor or according to local ART guidelines, the patient should initiate ART during the 8-week initial placebo or NSAID treatment phase.
11. Alcohol use: potential participant either self-reports or in the investigator's opinion that the patient drinks more than an average of four units/day over a usual week or is a binge drinker (men: 5 or more drinks; women: consume 4 or more drinks, in about 2 hours).
12. Major co-morbid conditions or any other finding which in the opinion of the investigator would compromise the protocol compliance or significantly influence the interpretation of results.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia

OTHER

Sponsor Role collaborator

Perinatal HIV Research Unit of the University of the Witswatersrand

OTHER

Sponsor Role collaborator

Fundació Institut Germans Trias i Pujol

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cristina Vilaplana, MD, PhD

Role: STUDY_CHAIR

Fundació Institut Germans Trias i Pujol

Locations

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National Center for Tuberculosis and Lung Diseases

Tbilisi, , Georgia

Site Status RECRUITING

Perinatal HIV Unit (PHRU)- Chris Hani Baragwanath Hospital

Soweto, Johannesburg, South Africa

Site Status RECRUITING

PHRU- Matlosana, Tshepong Hospital MDR Unit

Klerksdorp, Matlosana, South Africa

Site Status RECRUITING

Countries

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Georgia South Africa

Central Contacts

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Cristina Vilaplana, MD, PhD

Role: CONTACT

+34930330527

Lilibeth Arias de la Cruz

Role: CONTACT

+34934978681

Facility Contacts

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Sergo Vashakidze, MD, PhD

Role: primary

+995599236553

Neil Martinson, MBBCh MPH

Role: primary

+27 11 989 9700

Neil Martinson, MBBCh MPH

Role: primary

+27 11 989 9700

Tumelo Moloantoa

Role: backup

References

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Arias L, Otwombe K, Waja Z, Tukvadze N, Korinteli T, Moloantoa T, Fonseca KL, Pillay N, Seiphetlo T, Ouchi-Vernet D, Siles A, Carabias L, Quinones C, Vashakidze S, Martinson N, Vilaplana C. SMA-TB: study protocol for the phase 2b randomized double-blind, placebo-controlled trial to estimate the potential efficacy and safety of two repurposed drugs, acetylsalicylic acid and ibuprofen, for use as adjunct therapy added to, and compared with, the standard WHO recommended TB regimen. Trials. 2023 Jun 28;24(1):435. doi: 10.1186/s13063-023-07448-0.

Reference Type DERIVED
PMID: 37370174 (View on PubMed)

Related Links

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https://www.smatb.eu/

This CT is part of the project which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 847762.

https://cordis.europa.eu/project/id/847762

CORDIS -CE database -SMA-TB project description

Other Identifiers

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SMA-TB-001

Identifier Type: -

Identifier Source: org_study_id

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