Economic Evaluation of New MDR TB Regimens

NCT04207112 | Completed Phase 2 DMC

• 1 other identifier: PRACTECAL-EE
• Study Type: interventional
• Target: 73
• Locations: 3 countries
• Sites: 7

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.

Conditions

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

Keywords

Bedaquiline; Pretomanid; Linezolid; Clofazimine; Moxifloxacin; Economic Evaluation; Pharmacoeconomics

Outcome Measures

Primary Outcomes (2)

• 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.

  108 weeks post randomisation

• 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.

  108 weeks post randomisation

Secondary Outcomes (4)

• Mean cost per month of treatment

  108 weeks post randomisation

• Mean cost per course of treatment for different types of patients

  108 weeks post randomisation

• Incremental total cost of intervention for the trial population

  108 weeks post randomisation

• Incremental total cost of intervention for the modelling cohort

  108 weeks post randomisation

Study Arms (4)

Regimen 1: Bedaquiline, Pretomanid, Linezolid, Moxifloxacin

EXPERIMENTAL

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.

Drug: Bedaquiline; Drug: Pretomanid; Drug: Moxifloxacin; Drug: Linezolid

Regimen 2: Bedaquiline, Pretomanid, Linezolid, Clofazimine

EXPERIMENTAL

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

Drug: Bedaquiline; Drug: Pretomanid; Drug: Linezolid; Drug: Clofazimine

Regimen 3: Bedaquiline, Pretomanid, Linezolid

EXPERIMENTAL

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)

Drug: Bedaquiline; Drug: Pretomanid; Drug: Linezolid

Control regimen

ACTIVE COMPARATOR

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

Drug: Standard Drugs

Interventions

Bedaquiline DRUG

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.

Also known as: Sirturo, R207910, TMC207

Regimen 1: Bedaquiline, Pretomanid, Linezolid, Moxifloxacin; Regimen 2: Bedaquiline, Pretomanid, Linezolid, Clofazimine; Regimen 3: Bedaquiline, Pretomanid, Linezolid

Pretomanid DRUG

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.

Also known as: PA-824

Regimen 1: Bedaquiline, Pretomanid, Linezolid, Moxifloxacin; Regimen 2: Bedaquiline, Pretomanid, Linezolid, Clofazimine; Regimen 3: Bedaquiline, Pretomanid, Linezolid

Moxifloxacin DRUG

Moxifloxacin is an 8-methoxyquinolone class antimicrobial that is a potent inhibitor of DNA gyrase and topoisomerase IV in bacteria

Also known as: Avelox, BAY 12-8039

Regimen 1: Bedaquiline, Pretomanid, Linezolid, Moxifloxacin

Linezolid DRUG

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.

Also known as: Zyvox

Regimen 1: Bedaquiline, Pretomanid, Linezolid, Moxifloxacin; Regimen 2: Bedaquiline, Pretomanid, Linezolid, Clofazimine; Regimen 3: Bedaquiline, Pretomanid, Linezolid

Clofazimine DRUG

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.

Also known as: Lamprene

Regimen 2: Bedaquiline, Pretomanid, Linezolid, Clofazimine

Standard Drugs DRUG

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

Control regimen

Eligibility Criteria

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

You may qualify if:

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

Sponsors & Collaborators

• Medecins Sans Frontieres, Netherlands: lead
• London School of Hygiene and Tropical Medicine: collaborator
• Ministry of Health, Republic of Uzbekistan: collaborator
• Ministry of Public Health, Republic of Belarus: collaborator
• THINK TB & HIV Investigative Network: collaborator
• University of Liverpool: collaborator
• Wits Health Consortium (Pty) Ltd: collaborator

Study Sites (7)

Republican Scientific and Practical Centre for Pulmonology and Tuberculosis hospital

Minsk, Belarus

Location

Helen Joseph Hospital

Johannesburg, Gauteng, 2092, South Africa

Location

THINK Clinical Trial Unit, Hillcrest

Durban, KwaZulu-Natal, 3650, South Africa

Location

King DinuZulu Hospital

Durban, KwaZulu-Natal, 4091, South Africa

Location

Doris Goodwin Hospital

Pietermaritzburg, KwaZulu-Natal, South Africa

Location

Republican TB Hospital No. 2

Nukus, Karakalpakstan, Uzbekistan

Location

Sh Alimov Republican Specialised Scientific-Practical Medical Centre for Phthysiology and Pulmonology Hospital

Tashkent, Uzbekistan

Location

Related Publications (1)

• 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.

  PMID: 33039989 BACKGROUND

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant; Extensively Drug-Resistant Tuberculosis; Tuberculosis, Pulmonary

Interventions

bedaquiline; pretomanid; Moxifloxacin; Linezolid; Clofazimine

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Phenazines; Heterocyclic Compounds, 3-Ring

Study Officials

• Sedona Sweeny

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 20, 2019
• Study Start: October 20, 2020
• Primary Completion: August 25, 2022
• Study Completion: August 25, 2022
• Last Updated: April 22, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (4); UZ (2); BE (1)