Tuberculosis Multi Drug Resistant Active Clinical Trial
— DAZZLEOfficial title:
Prospective, Randomized, Open Label Phase 3 Study of the Efficacy and Tolerability of Delamanid, Linezolid, Pyrazinamide and Levofloxacin for Treatment of Patients With Fluoroquinolone-susceptible Multidrugresistant-‐Tuberculosis (MDR-TB)
| Verified date | September 2017 |
| Source | Boston University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The proposed study will randomize adults (18 years of age or older) with pulmonary MDR-TB
with sputum that contains M. tuberculosis that is isoniazid and rifampin resistant by
MTBDRplus and fluoroquinolone susceptible by MTBDRsl HIV seropositive (with or without
antiretroviral therapy) or negative (but not unknown) and Karnofsky score of >60 at sites in
Moldova, Peru, and the Philippines.
Patients with MDR-TB will be randomized to oral regimen of delamanid (DLM), linezolid (LZD),
levofloxacin (LFX) and pyrazinamide (PZA) for 24, 32, 40, 48 or 56 weeks or World Health
Organization (WHO) standard of care MDR-TB regimen (9-month "modified Bangladesh" regimen or
WHO standard MDR-TB regimen).
Primary Objective
1. Determine the shortest duration of the delamanid-containing oral regimen that is
non-inferior to the blended WHO standard regimen.
Secondary Objective
1. Define the safety and tolerability of the oral delamanid, linezolid, levofloxacin and
pyrazinamide regimen.
2. Determine if baseline PZA susceptibility is associated with shorter time to non-inferior
treatment duration.
3. Identify the relationship between delamanid and linezolid serum drug levels and time to
sputum culture conversion among patients on the delamanid-containing oral regimen.
4. Identify the relationship between delamanid and linezolid serum drug levels and
occurrence of adverse events among patients on the delamanid-containing oral regimen.
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | August 2022 |
| Est. primary completion date | August 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: 1. Men and women age =18 years 2. Subject has pulmonary TB 3. Sputum Smear, culture or Xpert MTB/RIF assay positive, with Hain MTBDRplus showing Rifampin (RIF) resistance and Isoniazid (INH) resistance and Hain MTBDRsl showing Fluoroquinolone susceptibility. 4. Patients within two weeks (=14 days) of starting second-line anti-TB drugs 5. HIV seropositive or seronegative but not unknown HIV serostatus. If the last documented negative HIV test was more than 3 months prior to randomization the current serostatus must be assessed. 6. Karnofsky score of > 60 (see Appendix B) at screening and randomization 7. Willingness by the patient to attend scheduled follow-up visits and undergo study assessments. 8. Women with child-bearing potential must agree to practice an adequate birth control or to abstain from heterosexual intercourse during study regimen. 9. Laboratory parameters (performed within 14 days prior to randomization): - Estimated Serum creatinine < 2.0 - Hemoglobin concentration = 7.0 g/dL - Platelet count of = 80,000/mm3 - Absolute neutrophil count (ANC) > 2000/ mm3 - Negative pregnancy test (for women of childbearing potential) during randomization/baseline - CD4 count if HIV infected (within 6 months) - Serum ALT and total bilirubin <3 times upper limit of normal - Serum albumin > 2.8 g/dL 10. Able to provide informed consent Exclusion Criteria: 1. Known quinolone-resistance 2. History of serotonin syndrome 3. History of symptomatic arrhythmia, or taking anti-arrhythmic agents 4. Previous treatment with delamanid or linezolid 5. Known allergy or intolerability to quinolone or pyrazinamide 6. Patients who are pregnant or who are unwilling to use proper contraceptives at childbearing age 7. Medical history of galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption 8. The need for ongoing use of prohibited drugs while on study drugs (see section 5.6 below) 9. History of optic neuropathy or peripheral neuropathy 10. History of hypersensitivity reaction to the study drugs 11. Patient is eligible for delamanid or bedaquiline under national program criteria |
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Boston University | University of Florida, Westat |
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Successful outcome at 18 months after randomization using culture results, follow up visits, | Successful outcome:if they have a -ve liq culture result 18 mos post rand not having been prev. classified as unsuccessful. If pt unable to produce sputum at 18 mos, the outcome will be classified as successful if they have a -ve culture at last visit at which they were able to produce sputum. Unsuccessful outcome: any of the foll occur, if patient 1)d/c from allocated study treatment & restarted on a diff MDR-TB regimen; 2)has surgery for MDR-TB; 3)treatment extended beyond the scheduled end of treatment for any reason other than making up of missed treatment; 4)restarted on MDR-TB treatment post the sched end of treatment; 5)Allocated treatment changed for any reason other than d/c of PZA when isolate is resistant to PZA; 6)death at any point up to 18 mos post-rand; 7)has a +ve sputum culture 8 wks before the sched completion; 8)has +ve sputum culture after culture conversion by dates specified in criterion number 7; 9)ltfu at any time post rand & before completion of the 18 mos f/u | 18 months | |
| Secondary | Secondary - Adverse Events | Adverse Events (AE) grade 3 and above, regardless of relatedness to drugs in the patient's MDR-TB treatment regimen | 18 months |