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Potential Efficacy and Safety of Using Adjunctive Ibuprofen for XDR-TB Tuberculosis (NSAIDS-XDRTB)

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ibuprofen
Standard of Care TB treatment
Sponsored by
Fundació Institut Germans Trias i Pujol
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculosis focused on measuring NSAIDS, tuberculosis treatment, anti-inflammatories, Host-directed therapies, TB

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Center for Tuberculosis and Lung Diseases
  • Perinatal HIV Unit (PHRU)

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control: Standard of Care TB treatment

Ibuprofen-treated

Arm Description

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

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

Outcomes

Primary Outcome Measures

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
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
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
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

Secondary Outcome Measures

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.
Proportion of pilot study participants showing differences in Health Quality of Life (HQoL).
Outcome measurements: HQoL measures at M2 and M6 relative to baseline.
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.

Full Information

First Posted
May 2, 2016
Last Updated
December 15, 2019
Sponsor
Fundació Institut Germans Trias i Pujol
Collaborators
National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia
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1. Study Identification

Unique Protocol Identification Number
NCT02781909
Brief Title
Potential Efficacy and Safety of Using Adjunctive Ibuprofen for XDR-TB Tuberculosis
Acronym
NSAIDS-XDRTB
Official Title
Pilot Study to Estimate the Potential Efficacy and Safety of Using Adjunctive Ibuprofen for the Treatment of XDR Tuberculosis
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
September 2016 (undefined)
Primary Completion Date
January 2019 (Actual)
Study Completion Date
January 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundació Institut Germans Trias i Pujol
Collaborators
National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
NSAIDS, tuberculosis treatment, anti-inflammatories, Host-directed therapies, TB

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control: Standard of Care TB treatment
Arm Type
Active Comparator
Arm Description
Individuals with confirmed pulmonary XDR-TB and receiving Standard of Care TB treatment according to national and WHO guidelines; n=12
Arm Title
Ibuprofen-treated
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Other Intervention Name(s)
NSAID
Intervention Description
Non-Steroid Anti-Inflammatory drug to be administered as adjunctive therapy
Intervention Type
Drug
Intervention Name(s)
Standard of Care TB treatment
Other Intervention Name(s)
anti-TB treatment
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of pilot study participants with microbiological efficacy-related events that are related to treatment.
Description
Number of pilot study participants with negative sputum culture at M2 and M6 following inclusion
Time Frame
6 months
Title
Number of pilot study participants with radiological efficacy-related events that are related to treatment.
Description
Changes detected by X-ray during follow-up up to month 6
Time Frame
6 months: at baseline, at month 3 and month 6
Title
Number of pilot study participants with clinical efficacy-related events that are related to treatment.
Description
Final treatment outcomes according to the WHO definitions including all time in follow-up to M6 on TB treatment
Time Frame
6 months
Title
Microbiological efficacy-related events: Time to stable culture conversion up to M6
Description
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
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Number of pilot study participants with Safety-related events.
Description
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.
Time Frame
6 months
Title
Proportion of pilot study participants showing differences in Health Quality of Life (HQoL).
Description
Outcome measurements: HQoL measures at M2 and M6 relative to baseline.
Time Frame
2 and 6 months
Title
Proportion of pilot study participants showing differences in Immune Responses at M2 and M6 relative to baseline.
Description
Outcome measurements: changes detected in immune responses at M2 and M6.
Time Frame
2 and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) Exclusion Criteria: 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 Pregnancy/Breastfeeding at inclusion 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cris Vilaplana, MD, PhD
Organizational Affiliation
Fundació Institut Germans Trias i Pujol
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Center for Tuberculosis and Lung Diseases
City
Tbilisi
Country
Georgia
Facility Name
Perinatal HIV Unit (PHRU)
City
Soweto
ZIP/Postal Code
1862,
Country
South Africa

12. IPD Sharing Statement

Links:
URL
https://unitatdetuberculosiexperimental.wordpress.com/
Description
Experimental Tuberculosis Unit of the Germans Trias i Pujol website (PI's affiliation)
URL
http://www.unza-uclms.org/hdt-net
Description
Host-Directed Therapies Network website

Learn more about this trial

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

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