Not provided
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The impact of the COVID-19 pandemic on TB diagnosis affected greatly the recruitment rate and posed challenges to the trial's timeline, consuming the funding needed to continue the enrolment.
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| Name | Class |
|---|---|
| National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia | OTHER |
| Perinatal HIV Research Unit of the University of the Witswatersrand | OTHER |
Not provided
Not provided
Not provided
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.
If eligible and informed consent obtained, patients will be randomized 1:1:1 into one of the following 3 arms, to receive:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Control group | Drug | placebo 2 months treatment: 2 tablets during 4 weeks + 1 tablet during 4 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to ≥ 67% Sustained Reduction in the TB Score | Time taken to reach 67% sustained reduction in the TB score over the course of TB treatment. Minimum value of the score = 0; Maximum value = 13). Higher scores mean a better or worse outcome. Difference between each intervention arm and control group were analysed. The TB Score has been described to be useful to monitor good response to TB treatment, regardless of HIV status. | 24 weeks of TB treatment |
| Time to Stable Culture Conversion (SCC) | Time to SCC is defined as the time until 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to a Stable Culture Conversion (SCC) at Week 8 and Week 16 After Treatment Initiation | Time to SCC is defined as the time until at least 2 consecutive negative cultures for M. tuberculosis at least 4 weeks apart. For this secondary outcome, differences between groups were analyzed at week 8 and week 16 | Week 8 and Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Safety 1: Serious Adverse Events Participant Proportion | Proportion of participants with at least one Serious Adverse Event by arm until the end of tuberculosis (TB) treatment, between each intervention arm and the control group. | Week 24 |
| Safety 2: Serious Adverse Event Rate Per Person Time |
Inclusion Criteria:
Exclusion Criteria:
Has a comorbid condition where treatment with aspirin, ibuprofen or other NSAID is indicated (e.g. cardiovascular disease, rheumatic fever, chronic pain, etc.)
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.
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:
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:
History or clinical record of sensitivity, asthma or allergy that could be attributed to NSAIDs
Weight < 45kg at baseline.
History or clinical record suggestive of any of the following in the past two years:
Patients with HIV infection (irrespective of ART status) if:
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).
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.
Not provided
Not provided
Not provided
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| Name | Affiliation | Role |
|---|---|---|
| Cristina Vilaplana, MD, PhD | Fundació Institut Germans Trias i Pujol | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Center for Tuberculosis and Lung Diseases | Tbilisi | Georgia | ||||
| Perinatal HIV Unit (PHRU)- Chris Hani Baragwanath Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37370174 | Background | 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. | |
| 23113626 |
| Label | URL |
|---|---|
| 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. | View source |
Not provided
205 were excluded mainly due to: lack of microbiological TB confirmation; HIV-related exclusion criteria; major comorbid conditions or investigator's decision; prior TB treatment; ALT/AST above threshold; body weight, haemoglobin or neutrophil below threshold; alcohol use; age outside the range; allergy to NSAIDs; use of antacids; proton pump inhibitors or immune-modulating therapy; multiple exclusion criteria.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. Control group: placebo 2 months treatment: 2 tablets during 4 weeks + 1 tablet during 4 weeks SoC TB: Standard of Care Tuberculosis treatment |
| FG001 | 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. ASA group: Acetylsalicylic acid 2 months treatment: 2 tablets during 4 weeks (600 mg daily) + 1 tablet during 4 weeks (300 mg daily) SoC TB: Standard of Care Tuberculosis treatment |
| FG002 | 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 IBU group: Ibuprofen 2 months treatment: 2 tablets during 4 weeks (800 mg daily) + 1 tablet during 4 weeks (400 mg daily) SoC TB: Standard of Care Tuberculosis treatment |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All participants randomized
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. Control group: placebo 2 months treatment: 2 tablets during 4 weeks + 1 tablet during 4 weeks SoC TB: Standard of Care Tuberculosis treatment |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to ≥ 67% Sustained Reduction in the TB Score | Time taken to reach 67% sustained reduction in the TB score over the course of TB treatment. Minimum value of the score = 0; Maximum value = 13). Higher scores mean a better or worse outcome. Difference between each intervention arm and control group were analysed. The TB Score has been described to be useful to monitor good response to TB treatment, regardless of HIV status. | Of the 221 participants enrolled, 204 participants had at least one post-baseline outcome assessment and are included in the outcome measure. 17 participants discontinued after baseline and had no post-baseline assessments. All collected data for the pre-specified outcome are reported in the outcome measure. | Posted | Median | 95% Confidence Interval | weeks | 24 weeks of TB treatment |
|
The whole study period (6 months after end of TB treatment)
Adverse events and serious adverse events were categorized according to the Medical Dictionary for Regulatory Activities and graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (version 2.1).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Control group: placebo 2 months treatment: 2 tablets during 4 weeks + 1 tablet during 4 weeks SoC TB: Standard of Care Tuberculosis treatment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute peritonitis | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatitis toxic drug-induced | Hepatobiliary disorders | MedDRA 10.0 | Systematic Assessment |
The trial was terminated because of financial and administrative constraints exacerbated by the COVID-19 pandemic.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Cristina Vilaplana, Head of the Experimental TB Unit | Fundació i Hospital Germans Trias i Pujol (IGTP-HUGTIP) | (+34) 93 033 0527 | 6401 | cvilaplana@igtp.cat |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jan 11, 2024 | Feb 19, 2025 | Prot_SAP_ICF_000.pdf |
Not provided
| ID | Term |
|---|---|
| D014397 | Tuberculosis, Pulmonary |
| D018088 | Tuberculosis, Multidrug-Resistant |
| D055985 | Latent Tuberculosis |
| D014376 | Tuberculosis |
| D003141 | Communicable Diseases |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D035061 | Control Groups |
| D001241 | Aspirin |
| D007052 | Ibuprofen |
| ID | Term |
|---|---|
| D015340 | Epidemiologic Research Design |
| D004812 | Epidemiologic Methods |
| D008919 | Investigative Techniques |
| D012107 | Research Design |
Not provided
Not provided
Multicentre, phase IIB, placebo controlled, randomized, 3-arm trial in DS and MDR TB patient
Not provided
Not provided
Not provided
| ASA group | Drug | Acetylsalicylic acid 2 months treatment: 2 tablets during 4 weeks (600 mg daily) + 1 tablet during 4 weeks (300 mg daily) |
|
|
| IBU group | Drug | Ibuprofen 2 months treatment: 2 tablets during 4 weeks (800 mg daily) + 1 tablet during 4 weeks (400 mg daily) |
|
|
| SoC TB | Drug | Standard of Care Tuberculosis treatment |
|
|
| Improvement or Resolution of Clinical Signs and Symptoms |
Signs and symptoms were assessed using the TB Score (TBS), which ranges from 0 to 13, with higher scores indicating more severe disease. The outcome was defined as the proportion of participants achieving a ≥50% reduction from baseline in TBS at Week 8 and a ≥75% reduction from baseline in TBS at Week 24. Comparisons were performed between each intervention arm and the control group. TBS has been described as a useful tool for monitoring clinical response to tuberculosis treatment. |
| Baseline, week 8 and week 24 |
| Improvement of Lung Function | Improvement of lung function in the 1-second forced expiratory volume (FEV1) | Baseline, week 8 and week 24 |
| Reduction of the Activity Component of the RTBES | Changes in chest X-ray (CXR) findings were assessed using the Activity component of the RUTI TB Evolution Score (RTBES). The baseline CXR served as the reference for comparison with subsequent CXRs obtained during tuberculosis treatment. The Activity component ranges from 0 to 38, with higher scores indicating more severe radiographic involvement. The outcome was defined as the proportion of participants achieving a ≥50% reduction from baseline in the Activity component at Week 8 and a ≥75% reduction from baseline at Week 24. Comparisons were performed between each intervention arm and the control group. | Baseline, week 8 and week 24 |
| Improvement of Health-related Quality of Life | Number of patients showing improvement in health-related quality of life at weeks 8 and 24 compared to baseline, as measured by the Saint Georges Respiratory Questionnaire (SGRQ). The SGRQ score ranges from 0 (best) to 100 (worst), with scores up to 7 considered to be within the healthy range. Improvement in this study being defined as achieving a score within the healthy range. | Baseline, week 8 and week 24 |
Serious adverse events rate expressed as events per 100-person week, starting the day of the first dose of NSAID or placebo until one month (30 days) after the last placebo or NSAID taken |
| Up to week 12 |
| Soweto |
| Johannesburg |
| 1864 |
| South Africa |
| PHRU- Matlosana, Tshepong Hospital MDR Unit | Klerksdorp | Matlosana | South Africa |
| Background |
| Rudolf F, Joaquim LC, Vieira C, Bjerregaard-Andersen M, Andersen A, Erlandsen M, Sodemann M, Andersen PL, Wejse C. The Bandim tuberculosis score: reliability and comparison with the Karnofsky performance score. Scand J Infect Dis. 2013 Apr;45(4):256-64. doi: 10.3109/00365548.2012.731077. Epub 2012 Oct 31. |
| 17852907 | Background | Wejse C, Gustafson P, Nielsen J, Gomes VF, Aaby P, Andersen PL, Sodemann M. TBscore: Signs and symptoms from tuberculosis patients in a low-resource setting have predictive value and may be used to assess clinical course. Scand J Infect Dis. 2008;40(2):111-20. doi: 10.1080/00365540701558698. |
| Background | Cuadras P, Rafart G, Català M, Arias L, Pérez R, Martinson N, Rosenthal A, Gabrielian A, Vashakidze S, Tenesa M, Bechini J, Vilaplana C. RTBES Radiological Index for Quantitative Assessment of Tuberculosis Evolution: Development and Validation. medRxiv 2025.02.14.25322286; doi:10.1101/2025.02.14.25322286. |
| Result | Arias L, Waja Z, Tukvadze N, Moloantoa T, Otwombe K, Korinteli T, Farrés J, Sopegno C, Gogichadze N, Fonseca KL, Pillay N, Seiphetlo T, Cardona PJ, Carabias L, Siles A, Llavero N, Quiñones C, McShane H, Hanekom W, Dyrhol-Riise AM, Karakousis PC, Charalambous S, Videla S, Vashakidze S, Martinson N, Vilaplana C. Acetylsalicylic Acid and Ibuprofen as Adjunctive Therapy for Tuberculosis. medRxiv 2025.12.01.25341191; doi:10.64898/2025.12.01.25341191 |
| CORDIS -CE database -SMA-TB project description | View source |
| SMA-TB repository | View source |
| Physician Decision |
|
| Lost to Follow-up |
|
| Relocation |
|
| Death |
|
| 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. ASA group: Acetylsalicylic acid 2 months treatment: 2 tablets during 4 weeks (600 mg daily) + 1 tablet during 4 weeks (300 mg daily) SoC TB: Standard of Care Tuberculosis treatment |
| BG002 | 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 IBU group: Ibuprofen 2 months treatment: 2 tablets during 4 weeks (800 mg daily) + 1 tablet during 4 weeks (400 mg daily) SoC TB: Standard of Care Tuberculosis treatment |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Drug susceptibility | Count of Participants | Participants |
|
| OG001 | 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. ASA group: Acetylsalicylic acid 2 months treatment: 2 tablets during 4 weeks (600 mg daily) + 1 tablet during 4 weeks (300 mg daily) SoC TB: Standard of Care Tuberculosis treatment |
| OG002 | 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 IBU group: Ibuprofen 2 months treatment: 2 tablets during 4 weeks (800 mg daily) + 1 tablet during 4 weeks (400 mg daily) SoC TB: Standard of Care Tuberculosis treatment |
|
|
|
| Primary | Time to Stable Culture Conversion (SCC) | Time to SCC is defined as the time until at least 2 consecutive negative cultures for M. tuberculosis at least 4 weeks apart during the first 24 weeks of TB treatment. | Of the 221 participants enrolled, 204 participants had at least one post-baseline outcome assessment and are included in the outcome measure. 17 participants discontinued after baseline and had no post-baseline assessments. All collected data for the pre-specified outcome are reported in the outcome measure. | Posted | Median | Inter-Quartile Range | weeks | 24 weeks of TB treatment |
|
|
|
|
| Secondary | Time to a Stable Culture Conversion (SCC) at Week 8 and Week 16 After Treatment Initiation | Time to SCC is defined as the time until at least 2 consecutive negative cultures for M. tuberculosis at least 4 weeks apart. For this secondary outcome, differences between groups were analyzed at week 8 and week 16 | Of the 221 participants enrolled, 204 participants had at least one post-baseline outcome assessment and are included in the outcome measure. 17 participants discontinued after baseline and had no post-baseline assessments. All collected data for the pre-specified outcome are reported in the outcome measure. | Posted | Median | 95% Confidence Interval | weeks | Week 8 and Week 16 |
|
|
|
|
| Secondary | Improvement or Resolution of Clinical Signs and Symptoms | Signs and symptoms were assessed using the TB Score (TBS), which ranges from 0 to 13, with higher scores indicating more severe disease. The outcome was defined as the proportion of participants achieving a ≥50% reduction from baseline in TBS at Week 8 and a ≥75% reduction from baseline in TBS at Week 24. Comparisons were performed between each intervention arm and the control group. TBS has been described as a useful tool for monitoring clinical response to tuberculosis treatment. | Of the 221 participants enrolled in the trial, 189 had TB score data available at baseline, week 8 and week 24 and were included in the secondary outcome analysis. 17 participants discontinued after baseline and had no post-baseline assessments. 15 participants did not have TB score data available at baseline, week 8 and/or week 24. All collected data for the pre-specified outcome are reported in the outcome measure. | Posted | Count of Participants | Participants | Baseline, week 8 and week 24 |
|
|
|
|
| Secondary | Improvement of Lung Function | Improvement of lung function in the 1-second forced expiratory volume (FEV1) | Our analysis was limited to participants from the Georgian site because lung function was assessed exclusively at that site. This population included DS and MDR participants. Of the 75 participants in the Georgian site, 54 had FEV1 data available at both baseline and week 24 and were included in this secondary outcome analysis. | Posted | Median | Inter-Quartile Range | FEV1 | Baseline, week 8 and week 24 |
|
|
|
|
| Secondary | Reduction of the Activity Component of the RTBES | Changes in chest X-ray (CXR) findings were assessed using the Activity component of the RUTI TB Evolution Score (RTBES). The baseline CXR served as the reference for comparison with subsequent CXRs obtained during tuberculosis treatment. The Activity component ranges from 0 to 38, with higher scores indicating more severe radiographic involvement. The outcome was defined as the proportion of participants achieving a ≥50% reduction from baseline in the Activity component at Week 8 and a ≥75% reduction from baseline at Week 24. Comparisons were performed between each intervention arm and the control group. | Of the 221 participants enrolled in the trial, 196 had activity component data of the RTBES available at both baseline and week 8, and 180 at baseline and week 24. All collected data for the pre-specified outcome are reported in the outcome measure and were included in the secondary outcome analysis. 17 participants discontinued after baseline and had no post-baseline assessments. 24 participants did not have activity component data of RTBES available at baseline, week 8 and/or week 24. | Posted | Count of Participants | Participants | Baseline, week 8 and week 24 |
|
|
|
|
| Secondary | Improvement of Health-related Quality of Life | Number of patients showing improvement in health-related quality of life at weeks 8 and 24 compared to baseline, as measured by the Saint Georges Respiratory Questionnaire (SGRQ). The SGRQ score ranges from 0 (best) to 100 (worst), with scores up to 7 considered to be within the healthy range. Improvement in this study being defined as achieving a score within the healthy range. | Of the 221 participants enrolled in the trial, 112 had SGRQ score data available at baseline and week 8 and 126 at baseline and week 24, and were included in the secondary outcome analysis. 17 participants discontinued after baseline and had no post-baseline assessments. 78 participants did not have SGRQ score data available at baseline, week 8 and/or week 24. All collected data for the pre-specified outcome are reported in the outcome measure. | Posted | Count of Participants | Participants | Baseline, week 8 and week 24 |
|
|
|
|
| Other Pre-specified | Safety 1: Serious Adverse Events Participant Proportion | Proportion of participants with at least one Serious Adverse Event by arm until the end of tuberculosis (TB) treatment, between each intervention arm and the control group. | All participants enrolled in the trial were included in the safety analysis (n=221). | Posted | Count of Participants | Participants | Week 24 |
|
|
|
| Other Pre-specified | Safety 2: Serious Adverse Event Rate Per Person Time | Serious adverse events rate expressed as events per 100-person week, starting the day of the first dose of NSAID or placebo until one month (30 days) after the last placebo or NSAID taken | All participants enrolled in the trial were included in the safety analysis (n=221). | Posted | Number | 95% Confidence Interval | events per 100-person week | Up to week 12 |
|
|
|
| 1 |
| 73 |
| 10 |
| 73 |
| 17 |
| 73 |
| EG001 | 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. ASA group: Acetylsalicylic acid 2 months treatment: 2 tablets during 4 weeks (600 mg daily) + 1 tablet during 4 weeks (300 mg daily) SoC TB: Standard of Care Tuberculosis treatment | 0 | 74 | 8 | 74 | 19 | 74 |
| EG002 | 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 IBU group: Ibuprofen 2 months treatment: 2 tablets during 4 weeks (800 mg daily) + 1 tablet during 4 weeks (400 mg daily) SoC TB: Standard of Care Tuberculosis treatment | 2 | 74 | 4 | 74 | 12 | 74 |
| Anaemia | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Toxic drug-induced hepatitis | Hepatobiliary disorders | MedDRA 10.0 | Systematic Assessment |
|
| TB Empyema | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Hydropneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Conjunctival deposit | Eye disorders | MedDRA 10.0 | Systematic Assessment |
|
| Acute gastroenteritis | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Death | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Arm fracture | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| TB spine | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Chest pain | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| TB complications | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA 10.0 | Systematic Assessment |
|
| TB treatment failure | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Hypertension | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
|
Not provided
Not provided
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000085343 | Latent Infection |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008722 | Methods |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010666 | Phenylpropionates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Title | Measurements |
|---|---|
|
| Multidrug-resistant TB |
|
| Regression, Cox |
| 0.5167 |
| Hazard Ratio (HR) |
| 1.123 |
| 2-Sided |
| 95 |
| 0.791 |
| 1.593 |
| Superiority |
|
| Regression, Cox |
| 0.2955 |
| Hazard Ratio (HR) |
| 1.266 |
| 2-Sided |
| 95 |
| 0.814 |
| 1.968 |
| Superiority |
| Testing the null hypothesis that there are no differences in the hazard ratio for time to Stable Sputum Culture Conversion (SCC) at week 16. | Regression, Cox | 0.7864 | Hazard Ratio (HR) | 1.051 | 2-Sided | 95 | 0.735 | 1.503 | Superiority |
| Testing the null hypothesis that there are no differences in the hazard ratio for time to Stable Sputum Culture Conversion (SCC) at week 16. | Regression, Cox | 0.4111 | Hazard Ratio (HR) | 1.163 | 2-Sided | 95 | 0.812 | 1.666 | Superiority |
| Title | Measurements |
|---|---|
|
| Risk Difference (RD) |
| 0.10 |
| 2-Sided |
| 95 |
| -0.06 |
| 0.25 |
| Superiority |
| Analysis of ≥75% improvement in TBS at Week 24 | Risk Difference (RD) | 0.03 | 2-Sided | 95 | -0.13 | 0.18 | Superiority |
| Analysis of ≥75% improvement in TBS at Week 24 | Risk Difference (RD) | 0.0 | 2-Sided | 95 | -0.16 | 0.16 | Superiority |
| Week 8 |
|
|
| Week 24 |
|
|
Mean Difference in FEV1 change from baseline to W8, between SoC+ASA and Control (estimated using cLDA).
| Superiority |
| Constrained longitudinal data analysis (cLDA) was fitted jointly on all 3 treatment arms (Control, SoC+ASA, SoC+IBU) and 3 timepoints (baseline, week 8 and week 24). Null hypothesis analysed here: no difference in FEV1 change from baseline to week 8 between SoC TB + IBU and Control. | Mixed Models Analysis | cLDA with random intercept and treatment-by-time interaction. Baseline constrained equal across arms. Model was fitted on 3 arms and 3 timepoints. | 0.979 | P-value for the treatment-by-time interaction SoC+IBU vs Control at week 8. Not adjusted for multiple comparisons. Threshold for statistical significance: 0.05. | Mean Difference (Final Values) | -0.002 | 2-Sided | 95 | -0.145 | 0.141 | Mean Difference in FEV1 change from baseline to W8, between SoC+IBU and Control (estimated using cLDA). | Superiority |
| Constrained longitudinal data analysis (cLDA) was fitted jointly on all 3 treatment arms (Control, SoC+ASA, SoC+IBU) and 3 timepoints (baseline, week 8 and week 24). Null hypothesis analysed here: no difference in FEV1 change from baseline to week 24 between SoC TB + ASA and Control. | Mixed Models Analysis | cLDA with random intercept and treatment-by-time interaction. Baseline constrained equal across arms. Model was fitted on 3 arms and 3 timepoints. | 0.408 | P-value for the treatment-by-time interaction SoC+ASA vs Control at week 24. Not adjusted for multiple comparisons. Threshold for statistical significance: 0.05. | Mean Difference (Final Values) | 0.060 | 2-Sided | 95 | -0.082 | 0.202 | Mean Difference in FEV1 change from baseline to W24, between SoC+ASA and Control (estimated using cLDA). | Superiority |
| Constrained longitudinal data analysis (cLDA) was fitted jointly on all 3 treatment arms (Control, SoC+ASA, SoC+IBU) and 3 timepoints (baseline, week 8 and week 24). Null hypothesis analysed here: no difference in FEV1 change from baseline to week 24 between SoC TB + IBU and Control. | Mixed Models Analysis | cLDA with random intercept and treatment-by-time interaction. Baseline constrained equal across arms. Model was fitted on 3 arms and 3 timepoints. | 0.654 | P-value for the treatment-by-time interaction SoC+IBU vs Control at week 24. Not adjusted for multiple comparisons. Threshold for statistical significance: 0.05. | Mean Difference (Final Values) | 0.034 | 2-Sided | 95 | -0.115 | 0.183 | Mean Difference in FEV1 change from baseline to W24, between SoC+IBU and Control (estimated using cLDA). | Superiority |
| Week 24 |
|
|
| Risk Difference (RD) |
| -0.15 |
| 2-Sided |
| 95 |
| -0.31 |
| 0.02 |
| Superiority |
| Risk Difference (RD) | 0.0 | 2-Sided | 95 | -0.16 | 0.16 | Superiority |
| Risk Difference (RD) | -0.07 | 2-Sided | 95 | -0.23 | 0.10 | Superiority |
| Week 24 |
|
|
| Risk Difference (RD) |
| 0.09 |
| 2-Sided |
| 95 |
| -0.13 |
| 0.29 |
| Superiority |
| Analysis of SGRQ improvement at Week 24 | Risk Difference (RD) | 0.09 | 2-Sided | 95 | -0.09 | 0.26 | Superiority |
| Analysis of SGRQ improvement at Week 24 | Risk Difference (RD) | 0.01 | 2-Sided | 95 | -0.17 | 0.19 | Superiority |