Potential Efficacy and Safety of Using Adjunctive Ibuprofen for XDR-TB Tuberculosis

Phase 2

Completed

• Conditions: Tuberculosis
• Interventions: Drug: Standard of Care TB treatment; Drug: Ibuprofen

• Registration Number: NCT02781909
• Lead Sponsor: Fundació Institut Germans Trias i Pujol

Brief Summary

Novel approaches to improve TB treatment outcomes (to reduce morbidity, mortality, and the duration of TB treatment) and to treat XDR-TB cases are urgently required. Host-Directed therapies (especially repurposed drugs such as Non-Steroid AntiInflammatory Drugs NSAIDS) could be useful in this context, and therefore the appropriateness and potential effect of this approach needs to be evaluated in humans. Investigators do propose a prospective, randomized, pilot study to estimate the potential efficacy and safety of using adjunctive ibuprofen for the treatment of XDR tuberculosis.

Detailed Description

There are a need for novel approaches to improve TB treatment outcomes (to reduce morbidity, mortality, and the duration of TB treatment) and to treat XDR-TB cases. Host-Directed therapies (especially repurposed drugs such as Non-Steroid AntiInflammatory Drugs NSAIDS) could be useful in this context, and therefore the appropriateness and potential effect of this approach needs to be evaluated in humans. Investigators do propose a prospective, randomized, pilot clinical trial to evaluate the potential efficacy and safety of using adjunctive ibuprofen during two months for the treatment of XDR tuberculosis.

Study Timeline

• Study First Submitted: 2016-05-02
• Study First Submitted QC: 2016-05-20
• Study First Posted: 2016-05-25
• Study Start: 2016-09
• Primary Completion: 2019-01
• Study Completion: 2019-01
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-15
• Last Update Posted: 2019-12-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Females and males aged ≥ 16
2. The patient must provide written informed consent
3. Females of childbearing potential (including females less than 2 years post- menopausal) must have a negative pregnancy test at enrolment and must agree to use highly effective methods of birth control
4. M.tuberculosis (Mtb) detected by culture with available drug susceptibility results for current isolate
5. XDR- TB confirmed by drug susceptibility testing (DST)

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:

1. Inability to provide written informed consent
2. First line drug treatment susceptible Mtb strain
3. Prior Treatment of either >3 days of TB treatment prior to randomization
4. Pregnancy/Breastfeeding at inclusion
5. Any of the following laboratory parameters: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN); total bilirubin > 2 x ULN; estimated glomerular filtration rate (eGFR) <60ml/hr; Neutrophil count ≤ 500 neutrophils / mm3; Platelet count < 50,000 cells / mm3
6. Receiving or anticipated to receive a daily dose of ≥ 10 mg of systemic prednisone or equivalent within the period starting 14 days prior to enrolment, or > 5 doses per week of any NSAID for ≥2 weeks in the month prior to randomization.
7. History of sensitivity or allergy to ibuprofen.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control: Standard of Care TB treatment	Standard of Care TB treatment	Individuals with confirmed pulmonary XDR-TB and receiving Standard of Care TB treatment according to national and WHO guidelines; n=12
Ibuprofen-treated	Standard of Care TB treatment	Individuals with confirmed pulmonary XDR-TB and receiving Standard of Care TB treatment according to national and WHO guidelines plus ibuprofen (400mg/day/2 months); n=12
Ibuprofen-treated	Ibuprofen	Individuals with confirmed pulmonary XDR-TB and receiving Standard of Care TB treatment according to national and WHO guidelines plus ibuprofen (400mg/day/2 months); n=12

Primary Outcome Measures

Name	Time	Method
Number of pilot study participants with microbiological efficacy-related events that are related to treatment.	6 months	Number of pilot study participants with negative sputum culture at M2 and M6 following inclusion
Number of pilot study participants with radiological efficacy-related events that are related to treatment.	6 months: at baseline, at month 3 and month 6	Changes detected by X-ray during follow-up up to month 6
Number of pilot study participants with clinical efficacy-related events that are related to treatment.	6 months	Final treatment outcomes according to the WHO definitions including all time in follow-up to M6 on TB treatment
Microbiological efficacy-related events: Time to stable culture conversion up to M6	6 months	Time to stable culture conversion up to M6: (≥ two consecutive cultures negative for M. tuberculosis) including all time in follow-up to month six on TB treatment. Differences between the two groups

Secondary Outcome Measures

Name	Time	Method
Proportion of pilot study participants showing differences in Health Quality of Life (HQoL).	2 and 6 months	Outcome measurements: HQoL measures at M2 and M6 relative to baseline.
Number of pilot study participants with Safety-related events.	6 months	Outcome measurements: incidence of safety-related events during the whole study period: clinical worsening of the disease, no sputum conversion (if AFS-), any worsening concerning vital parameters and routine blood work.
Proportion of pilot study participants showing differences in Immune Responses at M2 and M6 relative to baseline.	2 and 6 months	Outcome measurements: changes detected in immune responses at M2 and M6.

Trial Locations

Locations (2)

National Center for Tuberculosis and Lung Diseases; 🇬🇪 Tbilisi, Georgia

Perinatal HIV Unit (PHRU); 🇿🇦 Soweto, South Africa