Clinical Trial: An Open-label RCT to Evaluate a New Treatment Regimen for Patients With Multi-drug Resistant Tuberculosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Evaluating a New Treatment Regimen for Patients With Multidrug-resistant TB (MDR-TB) - a Prospective Open-label Randomised Controlled Trial

Brief 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 of 21-24 months treatment. 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.

Detailed Summary:

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 current 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 cons
Sponsor: University of Cape Town

Current Primary Outcome: Treatment success [ Time Frame: 24 months after initiation of treatment in either arm. ]

In the conventional arm treatment success is defined as the sum of cured or treatment completed cases. In the intervention arm treatment success is defined as the sum of cured and treatment completed cases, without subsequent relapse, re-infection or death during the 15-18 month follow up period.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Favourable outcome rate [ Time Frame: At 6-9 months for the intervention arm and 21-24 months for the conventional arm. ]
  • Time specific rate of treatment failure. [ Time Frame: 6-36 months ]
  • Time specific culture conversion proportions and rates. [ Time Frame: 6-36 months ]
  • Time specific relapse rate. [ Time Frame: 6-36 months. ]
  • Rate of re-infection. [ Time Frame: 6-36 months. ]
  • All cause mortality [ Time Frame: 0-36 months. ]
  • Composite measure of QT interval on ECG, grade 3 and 4 adverse events, stopping drugs Safety and tolerability end-points. [ Time Frame: 0-36 months. ]
  • Default rate [ Time Frame: 2-24 months ]
    Rate at which participants interrupt treatment for two or more consecutive months for any reason without medical approval.
  • Rate of loss of follow-up. [ Time Frame: 0-36 months. ]
    Rate at which a participant becomes untraceable at any point in the study, and remains untraceable at completion of study despite every effort being made by researchers to locate the participant.


Original Secondary Outcome:

  • Favourable outcome rate [ Time Frame: At 6 months for the intervention arm and 21-24 months for the conventional arm. ]
  • Time specific rate of treatment failure. [ Time Frame: 6-36 months ]
  • Time specific culture conversion rates. [ Time Frame: 6-36 months. ]
  • Time specific relapse rate. [ Time Frame: 12-36 months. ]
  • Rate of re-infection. [ Time Frame: 12-36 months. ]
  • All cause mortality [ Time Frame: 0-36 months. ]
  • Composite measure of QT interval on ECG, grade 3 and 4 adverse events, stopping drugs due to intolerance, adherence. [ Time Frame: 0-36 months. ]
    Safety and tolerability end-points.
  • Default rate [ Time Frame: 2-24 months ]
    Rate at which participants interrupt treatment for two or more consecutive months for any reason without medical approval.
  • Rate of loss of follow-up. [ Time Frame: 0-36 months. ]
    Rate at which a participant becomes untraceable at any point in the study, and remains untraceable at completion of study despite every effort being made by researchers to locate the participant.


Information By: University of Cape Town

Dates:
Date Received: May 22, 2015
Date Started: October 2015
Date Completion: January 2019
Last Updated: October 25, 2016
Last Verified: October 2016