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

Tuberculosis Clinical Trial

— NSAIDS-XDRTB  

Official title:

Pilot Study to Estimate the Potential Efficacy and Safety of Using Adjunctive Ibuprofen for the Treatment of XDR Tuberculosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02781909
• Other study ID #: NSAIDS4TB_01
• Status: Completed
• Phase: Phase 2
• Start date: September 2016
• Est. completion date: January 2019

Study information

• Verified date: December 2019
• Source: Fundació Institut Germans Trias i Pujol
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Drug:
• Ibuprofen
Non-Steroid Anti-Inflammatory drug to be administered as adjunctive therapy
• Standard of Care TB treatment
Standard of Care (SoC) TB Treatment will be optimized and drugs selected according to the National and WHO Guidelines, sensitivity profile and as per routine.

Locations

Country	Name	City	State
Georgia	National Center for Tuberculosis and Lung Diseases	Tbilisi
South Africa	Perinatal HIV Unit (PHRU)	Soweto

Sponsors (2)

Lead Sponsor	Collaborator
Fundació Institut Germans Trias i Pujol	National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia

Countries where clinical trial is conducted

Georgia,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of pilot study participants with microbiological efficacy-related events that are related to treatment.	Number of pilot study participants with negative sputum culture at M2 and M6 following inclusion	6 months
Primary	Number of pilot study participants with radiological efficacy-related events that are related to treatment.	Changes detected by X-ray during follow-up up to month 6	6 months: at baseline, at month 3 and month 6
Primary	Number of pilot study participants with clinical efficacy-related events that are related to treatment.	Final treatment outcomes according to the WHO definitions including all time in follow-up to M6 on TB treatment	6 months
Primary	Microbiological efficacy-related events: Time to stable culture conversion up to M6	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	6 months
Secondary	Number of pilot study participants with Safety-related events.	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.	6 months
Secondary	Proportion of pilot study participants showing differences in Health Quality of Life (HQoL).	Outcome measurements: HQoL measures at M2 and M6 relative to baseline.	2 and 6 months
Secondary	Proportion of pilot study participants showing differences in Immune Responses at M2 and M6 relative to baseline.	Outcome measurements: changes detected in immune responses at M2 and M6.	2 and 6 months

External Links

•   Experimental Tuberculosis Unit of the Germans Trias i Pujol website (PI's affiliation)
•   Host-Directed Therapies Network website