Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02454205 |
Other study ID # |
NExT-5001 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 2/Phase 3
|
First received |
|
Last updated |
|
Start date |
November 12, 2015 |
Est. completion date |
August 30, 2021 |
Study information
Verified date |
September 2021 |
Source |
University of Cape Town |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
This study aims to evaluate the impact of a new injection-free six-to-nine month treatment
regimen of linezolid, bedaquiline, levofloxacin, pyrazinamide (PZA) and ethionamide/high dose
isoniazid (INH) compared to the conventional empiric injection-based regimen. The secondary
aim is to determine if other treatment-related outcomes including adverse events, adherence
to treatment, culture conversion, and cure/completion are significantly different in the
intervention and conventional arms.
Description:
Background:
TB is completely out of control in South Africa and is now officially the most common cause
of death in this country. Alarmingly, the gravity if this pandemic has now been compounded by
the emergence of multidrug-resistant TB (MDR-TB), which constitutes resistance to the two
most potent anti-tuberculous drugs, namely rifampicin and isoniazid . XDR-TB refers to
resistance to rifampicin, isoniazid, any fluoroquinolone, and any second line injectable drug
(amikacin, kanamycin, or capreomycin). MDR-TB is a burgeoning epidemic in South Africa, with
rates trebling over the last decade. It is of considerable concern because mortality is high
(up to 50% in South Africa) and it often affects economically active young adults. It is also
a major threat to health care workers in South Africa. We recently showed a rate in SA health
care workers 6 fold higher than the general population further exacerbating the shortage of
this critical workforce in the country. The increasing cost to manage this disease is
unsustainable.
Although drug-resistant TB comprises less than 2% of the total caseload in the country
(approximately ½ million patients with TB treated per year), it consumes almost 40% of the
total national TB programme budget, and more than 60% of the total TB drug budget. This is
not sustainable and drug-resistant TB therefore has the capacity to destabilise functional TB
control programmes in many countries in Africa.
The treatment of MDR-TB is arduous, with a six to eight month intensive phase of daily
painful injections of Kanamycin combined with oral pyrazinamide, a fluoroquinolone
(moxifloxacin or levofloxacin), prothionamide and either cycloserine or para-aminosalicylic
acid (if cycloserine cannot be used). Treatment continues for 18 months after consecutive
negative sputum cultures, and lasts at least 20 months. There are substantial drug-associated
toxicities and adverse events that frequently lead to interruption or cessation of treatment.
This study proposes to test the efficacy of a new drug regimen for the treatment of MDR-TB
which is of short term duration and which does not contain an injectable drug, thus making
treatment easier to administer and thereby potentially increasing compliance. All the drugs
will be available to the NTP if the study is shown to be successful. This regimen will
comprise linezolid, bedaquiline, levofloxacin, PZA and either ethionamide or high dose INH or
teridazone. A gene-directed diagnostic approach (mutational analysis) will be used in the
interventional arm to individualise therapy and to inform on the use of high dose INH versus
ethionamide. If both mutations are present then to administer teridazone.
Furthermore, in the proposed study the key aim is to test a regimen (rather than an
individual drug) and will look at how the outcomes (24 month), including treatment
completion/cure (i.e. treatment success which is the primary outcome) and mortality, are
impacted. It is expected that introduction of a shortened effective regimen will reduce drop
out and drastically reduce mortality and on-going transmission. Moreover, the rates of XDR-TB
and TDR-TB may also decline.
The study will be conducted at 5 trial sites in South Africa that are designated MDR-TB
treatment facilities and it many cases patients will be recruited from the satellite clinics
of these centres reflecting the decentralized MDR-TB program. All the sites have the
necessary expertise and facilities to carry out the proposed study. The study is a fully
conceived and funded within South Africa.