Adjunctive Acetylsalicylic Acid and Ibuprofen for Tuberculosis

NCT04575519 | Recruiting Phase 2 DMC

• 1 other identifier: SMA-TB-001
• Study Type: interventional
• Target: 354
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

Tuberculosis, Pulmonary; Tuberculosis, MDR; Tuberculosis Infection

Keywords

Tuberculosis; Host-directed therapies; Infectious diseases; Drug-sensitive tuberculosis; Drug-resistant tuberculosis

Outcome Measures

Primary Outcomes (2)

• Time to ≥ 67% sustained reduction in the TB score

  Time to ≥ 67% sustained reduction in the TB score over the course of TB treatment

  Week 8 of follow-up

• Hazard ratio for time to stable culture conversion (SCC)

  Hazard ratio for time to stable culture conversion (SCC), at least 2 consecutive negative cultures for M. tuberculosis at least 4 weeks apart during the first 24 weeks of TB treatment.

  24 weeks of TB treatment

Secondary Outcomes (5)

• Hazard ratio for stable culture conversion (SCC) at week 8 and week 16 after treatment start.

  At week 8 and week 16

• Proportion of patients with improvement or resolution of clinical signs and symptoms at end of treatment (TB score).

  At week 24

• Proportion of patients with improvement of lung function impairment as change from baseline at week 8, 24 and end of treatment in the 1-second forced expiratory volume (FEV1) expressed as FEV1.

  At baseline, week 8 and week 24

• Changes in the BCN-SA Radiological Score Value.

  At baseline, week 8, week 24 (and month 12 if MDR)

• Number of patients with improvement of Health-related Quality of Life comparing baseline measure with that over the course of therapy.

  At week 8, week 24 and for MDR TB patients at the end of treatment

Other Outcomes (4)

• Safety 1: SAEs participant proportion.

  Up to month 6 in DS TB patients and up to month 20 in MDR TB patients

• Safety 2: SAEs in person time.

  Up to week 12

• Tolerability 1: permanent discontinuity proportion.

  Up to week 8

Study Arms (3)

Control group

ACTIVE COMPARATOR

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.

Drug: Control group; Drug: SoC TB

SoC TB + ASA group

EXPERIMENTAL

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.

Drug: ASA group; Drug: SoC TB

SoC TB + IBU group

EXPERIMENTAL

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

Drug: IBU group; Drug: SoC TB

Interventions

Control group DRUG

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

Also known as: placebo

Control group

ASA group DRUG

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

Also known as: Acetylsalicylic acid (ASA)

SoC TB + ASA group

IBU group DRUG

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

Also known as: Ibuprofen (IBU)

SoC TB + IBU group

SoC TB DRUG

Standard of Care Tuberculosis treatment

Also known as: Standard of Care Tuberculosis treatment

Control group; SoC TB + ASA group; SoC TB + IBU group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults, 18- 60 years of age
• Written informed consent in a language they understand. This includes informed consent to be in the trial and informed consent to collect specimens.
• Women of childbearing potential (including females \<2 years post-menopausal) must have a negative pregnancy test at enrolment.
• 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.

You may not qualify if:

• Has a comorbid condition where treatment with aspirin, ibuprofen or other NSAID is indicated (e.g. cardiovascular disease, rheumatic fever, chronic pain, etc.)
• 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.
• 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.
• 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
• 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
• History or clinical record of sensitivity, asthma or allergy that could be attributed to NSAIDs

Sponsors & Collaborators

• Fundació Institut Germans Trias i Pujol: lead
• National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia: collaborator
• Perinatal HIV Research Unit of the University of the Witswatersrand: collaborator

Study Sites (3)

National Center for Tuberculosis and Lung Diseases

Tbilisi, Georgia

RECRUITING

Perinatal HIV Unit (PHRU)- Chris Hani Baragwanath Hospital

Soweto, Johannesburg, 1864, South Africa

RECRUITING

PHRU- Matlosana, Tshepong Hospital MDR Unit

Klerksdorp, Matlosana, South Africa

RECRUITING

Related Publications (1)

• 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.

  PMID: 37370174 DERIVED

Related Links

• 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.
• CORDIS -CE database -SMA-TB project description
• SMA-TB repository

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant; Latent Tuberculosis; Tuberculosis; Communicable Diseases

Interventions

Control Groups; Aspirin; Ibuprofen

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Latent Infection; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Cristina Vilaplana, MD, PhD

  Fundació Institut Germans Trias i Pujol

  STUDY CHAIR

Central Study Contacts

Cristina Vilaplana, MD, PhD

CONTACT

+34930330527; cvilaplana@igtp.cat

Lilibeth Arias de la Cruz

CONTACT

+34934978681; larias@igtp.cat

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

Model Details: Multicentre, phase IIB, placebo controlled, randomized, 3-arm trial in DS and MDR TB patient

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: October 5, 2020
• Study Start: March 4, 2021
• Primary Completion: October 1, 2024
• Study Completion: June 1, 2025
• Last Updated: March 25, 2024

Record last verified: 2024-03

Locations

ZA (2); GE (1)