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

NCT02781909 | Completed Phase 2 DMC

• 1 other identifier: NSAIDS4TB_01
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 2

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.

Conditions

Tuberculosis

Keywords

NSAIDS; tuberculosis treatment; anti-inflammatories; Host-directed therapies; TB

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (3)

• Number of pilot study participants with Safety-related events.

  6 months

• Proportion of pilot study participants showing differences in Health Quality of Life (HQoL).

  2 and 6 months

• Proportion of pilot study participants showing differences in Immune Responses at M2 and M6 relative to baseline.

  2 and 6 months

Study Arms (2)

Control: Standard of Care TB treatment

ACTIVE COMPARATOR

Individuals with confirmed pulmonary XDR-TB and receiving Standard of Care TB treatment according to national and WHO guidelines; n=12

Drug: Standard of Care TB treatment

Ibuprofen-treated

EXPERIMENTAL

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

Drug: Ibuprofen; Drug: Standard of Care TB treatment

Interventions

Ibuprofen DRUG

Non-Steroid Anti-Inflammatory drug to be administered as adjunctive therapy

Also known as: NSAID

Ibuprofen-treated

Standard of Care TB treatment DRUG

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.

Also known as: anti-TB treatment

Control: Standard of Care TB treatment; Ibuprofen-treated

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Females and males aged ≥ 16
• The patient must provide written informed consent
• 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
• M.tuberculosis (Mtb) detected by culture with available drug susceptibility results for current isolate
• XDR- TB confirmed by drug susceptibility testing (DST)

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Inability to provide written informed consent
• First line drug treatment susceptible Mtb strain
• Prior Treatment of either \>3 days of TB treatment prior to randomization
• 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
• 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.
• History of sensitivity or allergy to ibuprofen.

Sponsors & Collaborators

• Fundació Institut Germans Trias i Pujol: lead
• National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia: collaborator

Study Sites (2)

National Center for Tuberculosis and Lung Diseases

Tbilisi, Georgia

Location

Perinatal HIV Unit (PHRU)

Soweto, 1862,, South Africa

Location

Related Links

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

MeSH Terms

Conditions

Tuberculosis

Interventions

Ibuprofen; Anti-Inflammatory Agents, Non-Steroidal

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents

Study Officials

• Cris Vilaplana, MD, PhD

  Fundació Institut Germans Trias i Pujol

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2016
• First Posted: May 25, 2016
• Study Start: September 1, 2016
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: December 17, 2019

Record last verified: 2019-12

Locations

ZA (1); GE (1)