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Economic Evaluation of New MDR TB Regimens (PRACTECAL-EE)

Primary Purpose

Multi-drug Resistant Tuberculosis, Extensively Drug-Resistant Tuberculosis, Pulmonary Tuberculoses

Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Bedaquiline
Pretomanid
Moxifloxacin
Linezolid
Clofazimine
Standard Drugs
Sponsored by
Medecins Sans Frontieres, Netherlands
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for Multi-drug Resistant Tuberculosis focused on measuring Bedaquiline, Pretomanid, Linezolid, Clofazimine, Moxifloxacin, Economic Evaluation, Pharmacoeconomics

Eligibility Criteria

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

Inclusion Criteria:

  • adults with Mycobacterium tuberculosis resistant to at least rifampicin by either molecular or phenotypic drug susceptibility test.

Exclusion Criteria:

-

Sites / Locations

  • Republican Scientific and Practical Centre for Pulmonology and Tuberculosis hospitalRecruiting
  • Helen Joseph HospitalRecruiting
  • Doris Goodwin HospitalRecruiting
  • THINK Clinical Trial Unit, HillcrestRecruiting
  • King DinuZulu HospitalRecruiting
  • Republican TB Hospital No. 2Recruiting
  • Sh Alimov Republican Specialised Scientific-Practical Medical Centre for Phthysiology and Pulmonology HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

Regimen 1: Bedaquiline, Pretomanid, Linezolid, Moxifloxacin

Regimen 2: Bedaquiline, Pretomanid, Linezolid, Clofazimine

Regimen 3: Bedaquiline, Pretomanid, Linezolid

Control regimen

Arm Description

Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Moxifloxacin: 400 mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated Drug: Bedaquiline Bedaquiline is a diarylquinoline class antimicrobial which blocks the proton pump for ATP synthase of mycobacteria. This in turn blocks the ATP production required for cellular energy production and leading to cell death.

Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated Clofazimine: 50 mg (less than 33 kg), 100 mg (more than 33 kg) for 24 weeks

Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated)

Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB

Outcomes

Primary Outcome Measures

Incremental cost incurred per disability adjusted life year (DALY) averted: Societal Perspective
Incremental cost incurred per disability adjusted life year (DALY) averted with the intervention regimen compared to the standard of care from societal perspective. DALYs will be modelled up to a life time horizon using a markov model.
Incremental cost per disability adjusted life year (DALY) averted: Provider Perspective
Incremental cost per disability adjusted life year (DALY) averted with the intervention regimen compared to the standard of care from provider perspective. DALYs will be modelled up to a life time horizon using a markov model.

Secondary Outcome Measures

Mean cost per month of treatment
Mean cost per month of treatment for different regimens and type of patient (MDR-TB, pre-XDR-TB (resistant to fluoroquinolone) and XDR-TB)
Mean cost per course of treatment for different types of patients
Mean cost per course of treatment for different types of patients (MDR-TB, pre-XDR-TB (resistant to fluoroquinolone), XDR-TB) and by category (training, monitoring, service delivery and drugs)
Incremental total cost of intervention for the trial population
Incremental total cost of intervention for the trial population, over the trial duration
Incremental total cost of intervention for the modelling cohort
Incremental total cost of intervention for the modelling cohort, over a life time horizon

Full Information

First Posted
December 3, 2019
Last Updated
May 12, 2021
Sponsor
Medecins Sans Frontieres, Netherlands
Collaborators
London School of Hygiene and Tropical Medicine, Ministry of Health, Republic of Uzbekistan, Ministry of Public Health, Republic of Belarus, THINK TB & HIV Investigative Network, University of Liverpool, Wits Health Consortium (Pty) Ltd, LSHTM Clinical Research Department
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1. Study Identification

Unique Protocol Identification Number
NCT04207112
Brief Title
Economic Evaluation of New MDR TB Regimens
Acronym
PRACTECAL-EE
Official Title
Economic Evaluation of New MDR TB Regimens (PRACTECAL EE)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Unknown status
Study Start Date
October 20, 2020 (Actual)
Primary Completion Date
July 30, 2022 (Anticipated)
Study Completion Date
July 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medecins Sans Frontieres, Netherlands
Collaborators
London School of Hygiene and Tropical Medicine, Ministry of Health, Republic of Uzbekistan, Ministry of Public Health, Republic of Belarus, THINK TB & HIV Investigative Network, University of Liverpool, Wits Health Consortium (Pty) Ltd, LSHTM Clinical Research Department

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The current treatment regimen for MDR-TB has poor outcomes and costs of treating MDR-TB are greater than treating drug susceptible TB, both in terms of health service and patient-incurred costs. Urgent action is needed to Identify short, effective and tolerable treatments for people with MDR-TB. The PRACTECAL economic evaluation sub-study (PRACTECAL-EE) will take place alongside the TB PRACTECAL trial, aiming to assess the costs to patients and providers of such regimens and to estimate the cost-effectiveness and poverty impact of an introduction of new MDR-TB regimens in the three countries participating in the main study.
Detailed Description
Multidrug resistant tuberculosis (MDR TB), tuberculosis (TB) that does not respond to at least isoniazid and rifampicin, is currently a public health issue. The current treatment regimen for MDR-TB has poor outcomes and costs of treating MDR-TB are greater than treating drug susceptible TB, both in terms of health service and patient-incurred costs. (1, 2). Key changes to recommendations for MDR-TB treatment regimens were published recently by the World Health Organization after an assessment of new evidence(3). In this rapid communication, three main changes to the standard MDR regimen were recommended: firstly, the withdrawal of injectable antibiotics; secondly, the inclusion of bedaquiline in a recommended longer regimen (ie 20 months); and thirdly, the recommendation of use for a shorter regimen only for specific conditions. It also highlights the urgent need for evidence to inform better optimal treatment choices for MDR-TB patients. Economic evaluations of such bedaquiline-containing regimens will provide additional important information for decision makers who need to consider its economic value along with clinical efficacy when planning for introduction. TB PRACTECAL is a randomised, controlled trial to evaluate the safety and efficacy of investigational regimens containing bedaquiline and pretomanid for the treatment of MDR-TB in adults. It has been designed in two stages: stage 1 is a phase II trial aiming to identify two regimens containing bedaquiline and pretomanid for further evaluation based on safety and efficacy outcomes after 8 weeks of treatment. Stage 2 is a phase III trial to evaluate the safety and efficacy of the two investigational regimens containing bedaquiline and pretomanid selected in stage 1 compared with the standard of care at 72 weeks post-randomisation (Clinical trial protocol, study number: NCT02589782). This economic evaluation sub-study (PRACTECAL EE) will take place alongside TB PRACTECAL aiming to assess the costs to patients and providers of such regimens and to estimate the cost-effectiveness and poverty impact of an introduction of new MDR-TB regimens in the three countries participating in the main study. The decision problem is stated as the evaluation of the new treatment regimen for MDR TB patients to inform the GRADE process at a global level, and health technology assessments (HTA) in the trial host countries, as applied to regimens for drug-resistant TB. During these processes (both at global level, GRADE, and at country level, HTA), the review of economic evidence produced alongside clinical trials focuses around patient outcomes and then on resources needed to answer the question of whether a new regimen should be considered for introduction. Population level considerations can also be included, especially in a second stage where the decision problem has advanced from whether to recommend a new regimen, to how to introduce it to achieve maximum health at a limited budget. The overall aim of this sub study is to estimate the probability that new MDR-TB regimens containing bedaquiline and pretomanid will be cost-effective from a societal as compared to the standard of care for MDR-TB patients in three settings: Uzbekistan, South Africa, and Belarus. A secondary aim is to assess the costs from a provider perspective of treating patients with these new regimens (new MDR-TB regimens containing bedaquiline and pretomanid), and estimate the impact of new regimens on prevalence of catastrophic costs due to TB. The specific objectives of this sub-study are, in each setting: to assess the costs from a provider's perspective for selected facilities in the intervention and control arms; to assess the costs from a patient's perspective for a sample of patients seeking care in study facilities in the intervention and control arms; To estimate the prevalence of catastrophic costs in the intervention and control arms; to assess the probability of new regimens being cost-effective at different willingness-to-pay thresholds from a societal perspective using a Markov model.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multi-drug Resistant Tuberculosis, Extensively Drug-Resistant Tuberculosis, Pulmonary Tuberculoses
Keywords
Bedaquiline, Pretomanid, Linezolid, Clofazimine, Moxifloxacin, Economic Evaluation, Pharmacoeconomics

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Regimen 1: Bedaquiline, Pretomanid, Linezolid, Moxifloxacin
Arm Type
Experimental
Arm Description
Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Moxifloxacin: 400 mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated Drug: Bedaquiline Bedaquiline is a diarylquinoline class antimicrobial which blocks the proton pump for ATP synthase of mycobacteria. This in turn blocks the ATP production required for cellular energy production and leading to cell death.
Arm Title
Regimen 2: Bedaquiline, Pretomanid, Linezolid, Clofazimine
Arm Type
Experimental
Arm Description
Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated Clofazimine: 50 mg (less than 33 kg), 100 mg (more than 33 kg) for 24 weeks
Arm Title
Regimen 3: Bedaquiline, Pretomanid, Linezolid
Arm Type
Experimental
Arm Description
Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated)
Arm Title
Control regimen
Arm Type
Active Comparator
Arm Description
Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB
Intervention Type
Drug
Intervention Name(s)
Bedaquiline
Other Intervention Name(s)
Sirturo, R207910, TMC207
Intervention Description
Bedaquiline is a diarylquinoline class antimicrobial which blocks the proton pump for ATP synthase of mycobacteria. This in turn blocks the ATP production required for cellular energy production and leading to cell death.
Intervention Type
Drug
Intervention Name(s)
Pretomanid
Other Intervention Name(s)
PA-824
Intervention Description
Pretomanid is an nitroimidazole class antimicrobial which interferes with cell wall biosynthesis in mycobacteria. It may have other mechanisms of action as well in non-replicating mycobacteria.
Intervention Type
Drug
Intervention Name(s)
Moxifloxacin
Other Intervention Name(s)
Avelox, BAY 12-8039
Intervention Description
Moxifloxacin is an 8-methoxyquinolone class antimicrobial that is a potent inhibitor of DNA gyrase and topoisomerase IV in bacteria
Intervention Type
Drug
Intervention Name(s)
Linezolid
Other Intervention Name(s)
Zyvox
Intervention Description
Linezolid, an oxazolidinone class antimicrobial which works by inhibiting ribosomal protein synthesis. It is approved for Gram-positive bacterial infections, and is increasingly being used for drug resistant TB disease.
Intervention Type
Drug
Intervention Name(s)
Clofazimine
Other Intervention Name(s)
Lamprene
Intervention Description
Clofazimine (Cfz) is a lipophilic riminophenazine licensed for treatment of leprosy. Its mechanism(s) of action remains unclear, but existing evidence suggests production of reactive oxygen species within Mycobacterium tuberculosis is one mechanism.
Intervention Type
Drug
Intervention Name(s)
Standard Drugs
Intervention Description
Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB.
Primary Outcome Measure Information:
Title
Incremental cost incurred per disability adjusted life year (DALY) averted: Societal Perspective
Description
Incremental cost incurred per disability adjusted life year (DALY) averted with the intervention regimen compared to the standard of care from societal perspective. DALYs will be modelled up to a life time horizon using a markov model.
Time Frame
108 weeks post randomisation
Title
Incremental cost per disability adjusted life year (DALY) averted: Provider Perspective
Description
Incremental cost per disability adjusted life year (DALY) averted with the intervention regimen compared to the standard of care from provider perspective. DALYs will be modelled up to a life time horizon using a markov model.
Time Frame
108 weeks post randomisation
Secondary Outcome Measure Information:
Title
Mean cost per month of treatment
Description
Mean cost per month of treatment for different regimens and type of patient (MDR-TB, pre-XDR-TB (resistant to fluoroquinolone) and XDR-TB)
Time Frame
108 weeks post randomisation
Title
Mean cost per course of treatment for different types of patients
Description
Mean cost per course of treatment for different types of patients (MDR-TB, pre-XDR-TB (resistant to fluoroquinolone), XDR-TB) and by category (training, monitoring, service delivery and drugs)
Time Frame
108 weeks post randomisation
Title
Incremental total cost of intervention for the trial population
Description
Incremental total cost of intervention for the trial population, over the trial duration
Time Frame
108 weeks post randomisation
Title
Incremental total cost of intervention for the modelling cohort
Description
Incremental total cost of intervention for the modelling cohort, over a life time horizon
Time Frame
108 weeks post randomisation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: adults with Mycobacterium tuberculosis resistant to at least rifampicin by either molecular or phenotypic drug susceptibility test. Exclusion Criteria: -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nicola James, MSc
Phone
+44 (0) 207 0674 255
Email
nicola.james@london.msf.org
First Name & Middle Initial & Last Name or Official Title & Degree
Charlotte Batts
Email
Charlotte.Batts@london.msf.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sedona Sweeny
Organizational Affiliation
London School of Hygiene and Tropical Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Republican Scientific and Practical Centre for Pulmonology and Tuberculosis hospital
City
Minsk
Country
Belarus
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ernest Nshimiyimana, MD
Phone
+375336486008
Email
minsk-ct-mtl@oca.msf.org
First Name & Middle Initial & Last Name & Degree
Varvara Solodovnikova, MD
Facility Name
Helen Joseph Hospital
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2092
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sharon Motlhako
Phone
+27 11 276 8800
Email
smotlhako@witshealth.co.za
First Name & Middle Initial & Last Name & Degree
Mohammed Rassool Rassool, MBChB
Facility Name
Doris Goodwin Hospital
City
Pietermaritzburg
State/Province
KwaZulu Natal
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Odette van Amsterdam
Phone
033 398 0054
Email
O.Amsterdam@think.org.za
First Name & Middle Initial & Last Name & Degree
Ronelle Moodliar, MBBS, MMed
Facility Name
THINK Clinical Trial Unit, Hillcrest
City
Durban
State/Province
KwaZulu-Natal
ZIP/Postal Code
3650
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seshni Moorgas
Phone
0317771009
Email
s.moorgas@think.org.za
First Name & Middle Initial & Last Name & Degree
Ronelle Moodliar, MBBS,MMed
Facility Name
King DinuZulu Hospital
City
Durban
State/Province
KwaZulu-Natal
ZIP/Postal Code
4091
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Londiwe Luthuli
Phone
+27 87 702 2581
Email
lluthuli@witshealth.co.za
First Name & Middle Initial & Last Name & Degree
Nosipho Ngubane, MBChB
Facility Name
Republican TB Hospital No. 2
City
Nukus
State/Province
Karakalpakstan
Country
Uzbekistan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Soe Moe, MD
Phone
+998939200344
Email
NukusCT-med2@oca.msf.org
First Name & Middle Initial & Last Name & Degree
Tigay N Zinaida, MD
Facility Name
Sh Alimov Republican Specialised Scientific-Practical Medical Centre for Phthysiology and Pulmonology Hospital
City
Tashkent
Country
Uzbekistan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pei Sun Aw, MD
Phone
+998 933881121
Email
tashkent-crc@oca.msf.org
First Name & Middle Initial & Last Name & Degree
Irina Liverko, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33039989
Citation
Sweeney S, Gomez G, Kitson N, Sinha A, Yatskevich N, Staples S, Moodliar R, Motlhako S, Maloma M, Rassool M, Ngubane N, Ndlovu E, Nyang'wa BT. Cost-effectiveness of new MDR-TB regimens: study protocol for the TB-PRACTECAL economic evaluation substudy. BMJ Open. 2020 Oct 10;10(10):e036599. doi: 10.1136/bmjopen-2019-036599.
Results Reference
background

Learn more about this trial

Economic Evaluation of New MDR TB Regimens

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