Clinical trial NCT02781909: Potential Efficacy and Safety of Using Adjunctive Ibuprofen for XDR-TB Tuberculosis
Official title: Pilot Study to Estimate the Potential Efficacy and Safety of Using Adjunctive Ibuprofen for the Treatment of XDR Tuberculosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: NSAIDS
tuberculosis treatment
anti-inflammatories
Host-directed therapies
TB
Lead sponsor: Fundació Institut Germans Trias i Pujol
Sponsor class: OTHER
Collaborators: name: National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia
First posted: 2016-05-25
Enrollment: 24
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of pilot study participants with microbiological efficacy-related events that are related to treatment.
timeFrame: 6 months
measure: Number of pilot study participants with radiological efficacy-related events that are related to treatment.
timeFrame: 6 months: at baseline, at month 3 and month 6
measure: Number of pilot study participants with clinical efficacy-related events that are related to treatment.
timeFrame: 6 months
measure: Microbiological efficacy-related events: Time to stable culture conversion up to M6
timeFrame: 6 months
Secondary outcomes:
measure: Number of pilot study participants with Safety-related events.
timeFrame: 6 months
measure: Proportion of pilot study participants showing differences in Health Quality of Life (HQoL).
timeFrame: 2 and 6 months
measure: Proportion of pilot study participants showing differences in Immune Responses at M2 and M6 relative to baseline.
timeFrame: 2 and 6 months
Other outcomes:
Locations:
city: Tbilisi
country: Georgia
facility: National Center for Tuberculosis and Lung Diseases
city: Soweto
country: South Africa
facility: Perinatal HIV Unit (PHRU)
Study officials:
affiliation: Fundació Institut Germans Trias i Pujol
name: Cris Vilaplana, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: