Clinical trial NCT04207112: Economic Evaluation of New MDR TB Regimens
Official title: Economic Evaluation of New MDR TB Regimens (PRACTECAL EE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Multi-drug Resistant Tuberculosis
Extensively Drug-Resistant Tuberculosis
Pulmonary Tuberculoses
Keywords: Bedaquiline
Pretomanid
Linezolid
Clofazimine
Moxifloxacin
Economic Evaluation
Pharmacoeconomics
Lead sponsor: Medecins Sans Frontieres, Netherlands
Sponsor class: OTHER
Collaborators: name: London School of Hygiene and Tropical Medicine
name: Ministry of Health, Republic of Uzbekistan
name: Ministry of Public Health, Republic of Belarus
name: THINK TB & HIV Investigative Network
name: University of Liverpool
name: Wits Health Consortium (Pty) Ltd
First posted: 2019-12-20
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

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:

1. to assess the costs from a provider's perspective for selected facilities in the intervention and control arms;
2. 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;
3. To estimate the prevalence of catastrophic costs in the intervention and control arms;
4. to assess the probability of new regimens being cost-effective at different willingness-to-pay thresholds from a societal perspective using a Markov model.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

-

Primary outcomes:
measure: Incremental cost incurred per disability adjusted life year (DALY) averted: Societal Perspective
timeFrame: 108 weeks post randomisation
measure: Incremental cost per disability adjusted life year (DALY) averted: Provider Perspective
timeFrame: 108 weeks post randomisation
Secondary outcomes:
measure: Mean cost per month of treatment
timeFrame: 108 weeks post randomisation
measure: Mean cost per course of treatment for different types of patients
timeFrame: 108 weeks post randomisation
measure: Incremental total cost of intervention for the trial population
timeFrame: 108 weeks post randomisation
measure: Incremental total cost of intervention for the modelling cohort
timeFrame: 108 weeks post randomisation
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: Republican Scientific and Practical Centre for Pulmonology and Tuberculosis hospital
city: Johannesburg
country: South Africa
facility: Helen Joseph Hospital
state: Gauteng
city: Pietermaritzburg
country: South Africa
facility: Doris Goodwin Hospital
state: KwaZulu Natal
city: Durban
country: South Africa
facility: THINK Clinical Trial Unit, Hillcrest
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: King DinuZulu Hospital
state: KwaZulu-Natal
city: Nukus
country: Uzbekistan
facility: Republican TB Hospital No. 2
state: Karakalpakstan
city: Tashkent
country: Uzbekistan
facility: Sh Alimov Republican Specialised Scientific-Practical Medical Centre for Phthysiology and Pulmonology Hospital
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Sedona Sweeny
role: PRINCIPAL_INVESTIGATOR
References:
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.