TABLE 2.
Emerging DR TB regimens: anticipated evidence pipeline from innovative clinical trials under way
| Type and name of trial (registry no.) | Drug regimen assessed and duration of treatment | Arm(s) | Phase(s) | Status | Timelines |
|---|---|---|---|---|---|
| 6-mo DR-TB regimens | |||||
| SimpliciTB trial (NCT03338621) | Safety and efficacy of BDQ, PTM, MFX, and PZA (BPaMZ) in DR-TB patients for 6 mo | Arm 1: drug-sensitive BPaMZ; Arm 2: drug-sensitive TB standard regimen; Arm 3: drug-resistant BPaMZ |
II and III | Fully enrolled; in follow-up stage | |
| TB PRACTECAL (NCT02589782) | Short-course regimen containing BDQ, PTM, and LZD ± MFX-CFZ for MDR-TB (6 mo) | Arm 1: regimen 1 (BDQ, PTM, MFX, and LZD); Arm 2: regimen 2 (BDQ, PTM, LZD, and CFZ); Arm 3: regimen 3 (BDQ, PTM, and LZD); Arm 4: control regimen (standard-of-care regimen for MDR/XDR-TB consistent with WHO guidelines) |
II and III | Recruitment terminated; analysis under way | 2017–2022 |
| ACTG A5312 (NCT01936831) | Different doses of INH and generic variants of INH-resistant M. tuberculosis (6 mo) | Arm 1: exptl arm, participants with inhA mutations receiving 5, 10, or 15 mg/kg of INH; Arm 2: exptl arm, participants with DS-TB receiving 5 mg/kg dose of INH; Arm 3: no-intervention arm, participants with katG mutation did not receive study drug |
II | Stage 1 completed; completed results available; stage 2 under way | 2014–2021 |
| 6- to 9-mo DR-TB regimens | |||||
| STREAM trial stage 2 (NCT02409290) | Comparing all-oral with BDQ or OBRa with BDQ and injectable (6–9 mo) | Arm 1: WHO-approved MDR-TB regimen in accordance with 2011 WHO MDR-TB treatment guidelines; Arm 2: regimen described by Van Deun (68), MFX replaced with LFX; Arm 3: all-oral regimen (BDQ, CFZ, EMB, LFX, and PZA) for 40 wks supplemented with INH and PTO for first 16 wks |
III | Fully enrolled; in follow-up stage | 2016–2022 |
| NExT (NCT02454205) | Injection-free regimen of BDQ, ethionamide, or high-dose INH, LZD, LFX, and PZA for 6–9 mo | Arm 1: active comparator, conventional treatment for 21–24 mo consisting of injectable agent; Arm 2: exptl, interventional treatment for 6–9 mo of all-oral regimen |
III | Completed | 2015–2021 |
| BEAT-TB, India (CTRI/2019/01/017310) | Short-course regimen (6–9 mo) for MDR-TB and resistance to FQ vs injectable of BDQ, DLM, LZD, LFX, and CFZ | Arm 1: intervention regimen (BDQ, DLM, LZD, CFZ) | IV | Open for enrollment (India) | 2019–2023 |
| ZeNix (NCT03086486) | Various doses and durations of LZD plus BDQ and PTM for XDR-TB, pre-XDR-TB, or complicated MDR-TB (>6 mo) | Arm 1: exptl regimen, 1,200 mg LZD for 26 wks, placebo LZD for 26 wks + PTM, BDQ; Arm 2: exptl regimen, 1,200 mg LZD for 9 wks, placebo LZD for 9 wks, PTM and BDQ; Arm 3: exptl regimen, 600 mg LZD for 26 wks, placebo LZD for 26 wks + PTM and BDQ; Arm 4: exptl regimen, 600 mg LZD for 9 wks, placebo LZD, PTM and LZD |
III | Results presented | 2017–2021 |
| 9-mo DR-TB regimens | |||||
| endTB (NCT02754765) | Shorter regimens containing BDQ and/or DLM, MFX-LFX and PZA, and LZD-CFZ for MDR/XDR-TB (9 mo) | Arm 1: endTB regimen 1 (BDQ, LZD, MFX and PZA); Arm 2: endTB regimen 2 (BDQ, LZD, CFZ, LFX, and PZA); Arm 3: endTB regimen 3 (BDQ, DLM, LZD, LFX, and PZA); Arm 4: endTB regimen 4 (DLM, LZD, CFZ, LFX, and PZA); Arm 5: endTB regimen 5 (DLM, CFZ, MFX, and PZA); Arm 6: endTB regimen 6 (control regimen; MDR-TB standard regimen consistent with WHO guidelines) |
III | Fully enrolled; in follow-up stage | 2016–2021 |
| BEAT-Tuberculosis, South Africa (NCT04062201) | Short-course regimen (6 mo) for MDR-TB consisting of BDQ, DLM, LZD, LFX, and CFZ vs standard of care (9-mo regimen) | Arm 1: exptl regimen, study strategy (BDQ, DLM, LZD, LFX, and CFZ); Arm 2: active comparator regimen, control strategy (MDR-TB standard-of-care regimen) |
III | Recruiting (South Africa) | 2019–2023 |
| 9- to 12-mo DR-TB regimens | |||||
| DELIBERATE ACTG 5343 (NCT02583048) | Drug-drug interactions and QT effect of BDQ and/or DLM regimens (9–12 mo) | Arm 1: BDQ + MDR-TB background regimen; Arm 2: DLM + MDR-TB background regimen; Arm 3: BDQ and DLM + MDR-TB background regimen |
II | Completed | 2016–2021 |
| EndTB-Q (NCT03896685) | BDQ, DLM, LZD, and CFZ for FQ-resistant MDR-TB (9–12 mo) | Arm 1: endTB-Q regimen (BDQ, DLM, CFZ, and LZD for 24 or 39 wks); Arm 2: endTB-Q control regimen (MDR-TB standard regimen consistent with WHO guidelines) |
III | Open for enrollment (Pakistan, India, Lesotho, Peru, and Vietnam) | 2020–2023 |
| MDR-END (NCT02619994) | Combination of DLM, LZD, LFX, and PZA for MDR-TB patients without FQ resistance (9–12 mo) vs 20–24 mo with injectables | Arm 1: control regimen (locally used WHO-approved MDR-TB regimen in Korea); Arm 2: exptl regimen (DLM, LZD, LFX, and PZA) |
II | Fully enrolled; in follow-up stage | 2016–2021 |
| Opti-Q (NCT01918397) | High-dose LFX (9–12 mo) | Arm 1: active comparator regimen, LFX 11 mg/kg daily and OBR Arm 2: exptl regimen, LFX 14 mg/kg daily and OBR; Arm 3: exptl regimen, LFX 17 mg/kg daily and OBR; Arm 4: exptl regimen, LFX 20 mg/kg daily and OBR |
II | Follow-up completed; currently analyzing results | 2015–2021 |
| DRAMATICb (NCT03828201) | Evaluating the safety and efficacy of all-oral regimen containing LFX, BDQ, LZD, DLM, and CFZ; patients to be randomized for different durations of treatment (study duration uncertain) | Arm 1: exptl regimen, DRAMATIC-16 wks (DLM, LFX, BDQ, CFZ, and LZD) Arm 2: exptl regimen, DRAMATIC-24 wks (DLM, LFX, BDQ, CFZ, and LZD) Arm 3: exptl regimen, DRAMATIC-32 wks (DLM, LFX, BDQ, CFZ, and LZD) Arm 4: exptl regimen; DRAMATIC-40 wks (DLM, LFX, BDQ, CFZ, and LZD) |
II | Recruiting | 2021–2025 |
a
OBR, optimized background regimen. Abbreviations for drug names are provided in Table 1, footnote a.
b
DRAMATIC, Duration-Randomized Study of Treatment of Patients with MDR-TB.