Tuberculosis Multi Drug Resistant ActivePhase 3DAZZLENCT02975570
Efficacy and Tolerability of Delamanid, Linezolid, Pyrazinamide and Levofloxacin
A Phase 3 study testing Delamanid, Linezolid and Levofloxacin in people with Tuberculosis Multi Drug Resistant Active, run by Boston University.
Trial summary
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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis Multi Drug Resistant Active
- What is being tested?
- Delamanid, Linezolid and Levofloxacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Aug 2017to Aug 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women age ≥18 years
- Subject has pulmonary TB
- 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.
- Patients within two weeks (≤14 days) of starting second-line anti-TB drugs
- 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.
- Karnofsky score of > 60 (see Appendix B) at screening and randomization
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- Willingness by the patient to attend scheduled follow-up visits and undergo study assessments.
- Women with child-bearing potential must agree to practice an adequate birth control or to abstain from heterosexual intercourse during study regimen.
- 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
- Able to provide informed consent
Who cannot join
- Known quinolone-resistance
- History of serotonin syndrome
- History of symptomatic arrhythmia, or taking anti-arrhythmic agents
- Previous treatment with delamanid or linezolid
- Known allergy or intolerability to quinolone or pyrazinamide
- Patients who are pregnant or who are unwilling to use proper contraceptives at childbearing age
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- Medical history of galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption
- The need for ongoing use of prohibited drugs while on study drugs (see section 5.6 below)
- History of optic neuropathy or peripheral neuropathy
- History of hypersensitivity reaction to the study drugs
- Patient is eligible for delamanid or bedaquiline under national program criteria
About this study
Official 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)
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).
Read more
Primary Objective
- Determine the shortest duration of the delamanid-containing oral regimen that is non-inferior to the blended WHO standard regimen.
Secondary Objective
- Define the safety and tolerability of the oral delamanid, linezolid, levofloxacin and pyrazinamide regimen.
- Determine if baseline PZA susceptibility is associated with shorter time to non-inferior treatment duration.
- Identify the relationship between delamanid and linezolid serum drug levels and time to sputum culture conversion among patients on the delamanid-containing oral regimen.
- Identify the relationship between delamanid and linezolid serum drug levels and occurrence of adverse events among patients on the delamanid-containing oral regimen.
Read the detailed description
Multidrug-resistant tuberculosis (MDR-TB) is tuberculosis that is resistant to at least isoniazid and rifampicin, the two most important anti-TB drugs. WHO has estimated that over 480,000 new cases of MDR-TB occurred in 127 countries in 2014, causing 150,000 deaths; this represents a 70% increase in the number of cases since 2000. MDR-TB cure rates are substantially lower than the 85+% cure expected in drug-susceptible TB. The MDR-TB treatment regimen currently recommended by WHO includes at least 4 second-line drugs plus PZA for 18-24 months, including an injectable agent for the induction phase of 6-8 month. However, the average global success rate of such treatment among patients treated in TB programs is only 50%. More recently, an alternative treatment regimen, known as the "Bangladesh" regimen, has become available.This regimen uses 7 drugs given for 9 months but still includes an injectable agent, which is the cause of the most common and severe toxicities seen when treating MDR-TB. In selected patients this regimen has been able to achieve over 80% cures, but use has been restricted to geographic areas where previous use of second-line drugs is rare. Alternatives will be necessary for other settings and patients with prior second-line drug exposure.
Treatment-limiting side effects are common when using second-line drugs for long periods of time. Overall, 69-73% of patients with MDR-TB treated with the WHO standard regimen are reported to have experienced at least one side effect, and 29%-55% discontinued one or more study drugs because of inability to tolerate a drug. The Bangladesh regimen also has substantial toxicity, with 63% of participants experiencing adverse drug reactions in one report. Thus, while this regimen is shorter and slightly better tolerated than the WHO standard regimen, it still does not provide an easily tolerated alternative, largely because it contains an injectable agent.
The 20-24 month regimen currently in use exposes patients to drug toxicity over prolonged periods of time and demands substantial human resources. Patients receiving these regimens require two years of directly observed therapy with careful monitoring for drug toxicity. Reduction in the duration of treatment would free up program staff to treat additional MDR-TB patients. Development of a shorter treatment regimen will greatly enhance the ability of programs to keep up with the anticipated increase in patients needing treatment.
This application proposes a study to determine whether the 9-month oral regime that uses Delaminid, Linezolid, Levofloxacin and Pyrazinamide is as good as the current WHO standard of care regimen.
The study proposes to randomize approximately 300 adults in Peru, Moldova and Phillipines where MDR-TB is common.
- Conditions
- Tuberculosis Multi Drug Resistant Active
- Being tested
- Delamanid, Linezolid, Levofloxacin, Pyrazinamide, WHO MDR-TB regimen
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DelamanidDrug
Also called Deltyba
Delamanid is a medication used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active multidrug-resistant tuberculosis. It is taken by mouth.
LinezolidDrug
Also called Zyvox
Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics.
LevofloxacinDrug
Also called Levaquin
Levoflaxacin is an antibiotic used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, urinary tract infections, chronic prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis.
PyrazinamideDrug
Also called Zinamide
Pyrazinamide is a medication used in combination with other drugs such as isoniazid and rifampicin in the treatment of Mycobacterium tuberculosis.
WHO MDR-TB regimenDrug
Also called 5-agent treatment regimen for MDR-TB
The WHO guidelines recommend the following 5-agent treatment regimen for MDR-TB: pyrazinamide; a fluoroquinolone; a parenteral agent (typically amikacin or kanamycin); ethionamide (or prothionamide); and either cycloserine or para-aminosalicylic acid, with preference for cycloserine. Short (9 mos) or longer (20-24 mos) treatment schedules can be used.
| Study group | Role | What they receive |
|---|---|---|
| DAZZLE-24 wks | Experimental | Delamanid, Linezolid, Levofloxacin, Pyrazinamide (DAZZLE) treatment regimen- delamanid 100 mg PO BID, linezolid 600 mg PO QD, levofloxacin 1000 mg PO QD, and pyrazinamide 20-30 mg/Kg PO QD for 24 weeks, with linezolid dose reduction to 300 mg daily after 16 weeks (these doses are the usual doses for treatment of TB for all 4 study agents). Receives: Drug: Delamanid; Drug: Linezolid; Drug: Levofloxacin; Drug: Pyrazinamide |
| DAZZLE-32 wks | Experimental | Delamanid, Linezolid, Levofloxacin, Pyrazinamide (DAZZLE) delamanid 100 mg PO BID, linezolid 600 mg PO QD, levofloxacin 1000 mg PO QD, and pyrazinamide 20-30 mg/Kg PO QD for 32 weeks, with linezolid dose reduction to 300 mg daily after 16 weeks (these doses are the usual doses for treatment of TB for all 4 study agents). Receives: Drug: Delamanid; Drug: Linezolid; Drug: Levofloxacin; Drug: Pyrazinamide |
| DAZZLE-40 wks | Experimental | Delamanid, Linezolid, Levofloxacin, Pyrazinamide (DAZZLE) treatment regimen: delamanid 100 mg PO BID, linezolid 600 mg PO QD, levofloxacin 1000 mg PO QD, and pyrazinamide 20-30 mg/Kg PO QD for 40 weeks, with linezolid dose reduction to 300 mg daily after 16 weeks (these doses are the usual doses for treatment of TB for all 4 study agents). Receives: Drug: Delamanid; Drug: Linezolid; Drug: Levofloxacin; Drug: Pyrazinamide |
| DAZZLE-48 wks | Experimental | Delamanid, Linezolid, Levofloxacin, Pyrazinamide (DAZZLE) treatment regimen- delamanid 100 mg PO BID, linezolid 600 mg PO QD, levofloxacin 1000 mg PO QD, and pyrazinamide 20-30 mg/Kg PO QD for 48 weeks, with linezolid dose reduction to 300 mg daily after 16 weeks (these doses are the usual doses for treatment of TB for all 4 study agents). Receives: Drug: Delamanid; Drug: Linezolid; Drug: Levofloxacin; Drug: Pyrazinamide |
| DAZZLE-56 wks | Experimental | Delamanid, Linezolid, Levofloxacin, Pyrazinamide (DAZZLE) treatment regimen- delamanid 100 mg PO BID, linezolid 600 mg PO QD, levofloxacin 1000 mg PO QD, and pyrazinamide 20-30 mg/Kg PO QD for 56 weeks, with linezolid dose reduction to 300 mg daily after 16 weeks (these doses are the usual doses for treatment of TB for all 4 study agents). Receives: Drug: Delamanid; Drug: Linezolid; Drug: Levofloxacin; Drug: Pyrazinamide |
| WHO MDR-TB regimen- 9 mos or 20-24 mos | Active comparator | MDR-TB treatment with 9-month or 20-24 month WHO approved regimen. The WHO guidelines recommend the following 5-agent treatment regimen for MDR-TB: pyrazinamide; a fluoroquinolone; a parenteral agent (typically amikacin or kanamycin); ethionamide (or prothionamide); and either cycloserine or para-aminosalicylic acid, with preference for cycloserine. Receives: Drug: WHO MDR-TB regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 18 months
Secondary outcomes (1)
Secondary - Adverse Events
Adverse Events (AE) grade 3 and above, regardless of relatedness to drugs in the patient's MDR-TB treatment regimen
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2016 (estimated)
- Study startAug 2017 (estimated)
- Primary completionAug 2021 (estimated)
- Study completionAug 2022 (estimated)
Why it stopped: The study could not be conducted since funding was not obtained.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis Multi Drug Resistant ActiveStudies of the same condition, open and under way.
- More trials run by Boston UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston University
- Sponsor type
- University, hospital or other
- Collaborators
- Westat, University of Florida
- Responsible party
- Principal investigator, Charles R Horsburgh, Boston University
- Investigators
- C. Robert Horsburgh, MD, Principal investigator, Boston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02975570
- Sponsor's protocol ID
- H-36160
- Acronym
- DAZZLE
- Status last verified
- Sep 2017
- First submitted
- 21 Oct 2016
- Last updated
- 11 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT02975570
- Acronym / sponsor ID
- DAZZLE / H-36160
- Conditions
- Tuberculosis Multi Drug Resistant Active
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study could not be conducted since funding was not obtained.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Boston UniversityUniversity, hospital or other
- Collaborators
- Westat, University of Florida
- Study start
- Aug 2017 (estimated)
- Primary completion
- Aug 2021 (estimated)
- Study completion
- Aug 2022 (estimated)
- First posted
- 29 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Determine the shortest duration of the delamanid-containing oral regimen that is non-inferior to the blended WHO standard regimen.
Secondary Objective
- Define the safety and tolerability of the oral delamanid, linezolid, levofloxacin and pyrazinamide regimen.
- Determine if baseline PZA susceptibility is associated with shorter time to non-inferior treatment duration.
- Identify the relationship between delamanid and linezolid serum drug levels and time to sputum culture conversion among patients on the delamanid-containing oral regimen.
- Identify the relationship between delamanid and linezolid serum drug levels and occurrence of adverse events among patients on the delamanid-containing oral regimen.
Detailed description
Multidrug-resistant tuberculosis (MDR-TB) is tuberculosis that is resistant to at least isoniazid and rifampicin, the two most important anti-TB drugs. WHO has estimated that over 480,000 new cases of MDR-TB occurred in 127 countries in 2014, causing 150,000 deaths; this represents a 70% increase in the number of cases since 2000. MDR-TB cure rates are substantially lower than the 85+% cure expected in drug-susceptible TB. The MDR-TB treatment regimen currently recommended by WHO includes at least 4 second-line drugs plus PZA for 18-24 months, including an injectable agent for the induction phase of 6-8 month. However, the average global success rate of such treatment among patients treated in TB programs is only 50%. More recently, an alternative treatment regimen, known as the "Bangladesh" regimen, has become available.This regimen uses 7 drugs given for 9 months but still includes an injectable agent, which is the cause of the most common and severe toxicities seen when treating MDR-TB. In selected patients this regimen has been able to achieve over 80% cures, but use has been restricted to geographic areas where previous use of second-line drugs is rare. Alternatives will be necessary for other settings and patients with prior second-line drug exposure.
Treatment-limiting side effects are common when using second-line drugs for long periods of time. Overall, 69-73% of patients with MDR-TB treated with the WHO standard regimen are reported to have experienced at least one side effect, and 29%-55% discontinued one or more study drugs because of inability to tolerate a drug. The Bangladesh regimen also has substantial toxicity, with 63% of participants experiencing adverse drug reactions in one report. Thus, while this regimen is shorter and slightly better tolerated than the WHO standard regimen, it still does not provide an easily tolerated alternative, largely because it contains an injectable agent.
The 20-24 month regimen currently in use exposes patients to drug toxicity over prolonged periods of time and demands substantial human resources. Patients receiving these regimens require two years of directly observed therapy with careful monitoring for drug toxicity. Reduction in the duration of treatment would free up program staff to treat additional MDR-TB patients. Development of a shorter treatment regimen will greatly enhance the ability of programs to keep up with the anticipated increase in patients needing treatment.
This application proposes a study to determine whether the 9-month oral regime that uses Delaminid, Linezolid, Levofloxacin and Pyrazinamide is as good as the current WHO standard of care regimen.
The study proposes to randomize approximately 300 adults in Peru, Moldova and Phillipines where MDR-TB is common.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| DAZZLE-24 wks | Experimental | Drug: Delamanid, Drug: Linezolid, Drug: Levofloxacin, Drug: PyrazinamideDelamanid, Linezolid, Levofloxacin, Pyrazinamide (DAZZLE) treatment regimen- delamanid 100 mg PO BID, linezolid 600 mg PO QD, levofloxacin 1000 mg PO QD, and pyrazinamide 20-30 mg/Kg PO QD for 24 weeks, with linezolid dose reduction to 300 mg daily after 16 weeks (these doses are the usual doses for treatment of TB for all 4 study agents). |
| DAZZLE-32 wks | Experimental | Drug: Delamanid, Drug: Linezolid, Drug: Levofloxacin, Drug: PyrazinamideDelamanid, Linezolid, Levofloxacin, Pyrazinamide (DAZZLE) delamanid 100 mg PO BID, linezolid 600 mg PO QD, levofloxacin 1000 mg PO QD, and pyrazinamide 20-30 mg/Kg PO QD for 32 weeks, with linezolid dose reduction to 300 mg daily after 16 weeks (these doses are the usual doses for treatment of TB for all 4 study agents). |
| DAZZLE-40 wks | Experimental | Drug: Delamanid, Drug: Linezolid, Drug: Levofloxacin, Drug: PyrazinamideDelamanid, Linezolid, Levofloxacin, Pyrazinamide (DAZZLE) treatment regimen: delamanid 100 mg PO BID, linezolid 600 mg PO QD, levofloxacin 1000 mg PO QD, and pyrazinamide 20-30 mg/Kg PO QD for 40 weeks, with linezolid dose reduction to 300 mg daily after 16 weeks (these doses are the usual doses for treatment of TB for all 4 study agents). |
| DAZZLE-48 wks | Experimental | Drug: Delamanid, Drug: Linezolid, Drug: Levofloxacin, Drug: PyrazinamideDelamanid, Linezolid, Levofloxacin, Pyrazinamide (DAZZLE) treatment regimen- delamanid 100 mg PO BID, linezolid 600 mg PO QD, levofloxacin 1000 mg PO QD, and pyrazinamide 20-30 mg/Kg PO QD for 48 weeks, with linezolid dose reduction to 300 mg daily after 16 weeks (these doses are the usual doses for treatment of TB for all 4 study agents). |
| DAZZLE-56 wks | Experimental | Drug: Delamanid, Drug: Linezolid, Drug: Levofloxacin, Drug: PyrazinamideDelamanid, Linezolid, Levofloxacin, Pyrazinamide (DAZZLE) treatment regimen- delamanid 100 mg PO BID, linezolid 600 mg PO QD, levofloxacin 1000 mg PO QD, and pyrazinamide 20-30 mg/Kg PO QD for 56 weeks, with linezolid dose reduction to 300 mg daily after 16 weeks (these doses are the usual doses for treatment of TB for all 4 study agents). |
| WHO MDR-TB regimen- 9 mos or 20-24 mos | Active comparator | Drug: WHO MDR-TB regimenMDR-TB treatment with 9-month or 20-24 month WHO approved regimen. The WHO guidelines recommend the following 5-agent treatment regimen for MDR-TB: pyrazinamide; a fluoroquinolone; a parenteral agent (typically amikacin or kanamycin); ethionamide (or prothionamide); and either cycloserine or para-aminosalicylic acid, with preference for cycloserine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Men and women age ≥18 years
- Subject has pulmonary TB
- 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.
- Patients within two weeks (≤14 days) of starting second-line anti-TB drugs
- 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.
Key exclusion criteria (11 listed)
- Known quinolone-resistance
- History of serotonin syndrome
- History of symptomatic arrhythmia, or taking anti-arrhythmic agents
- Previous treatment with delamanid or linezolid
- Known allergy or intolerability to quinolone or pyrazinamide
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DelamanidAlso: DeltybaDelamanid is a medication used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active multidrug-resistant tuberculosis. It is taken by mouth. | Drug | DAZZLE-24 wks, DAZZLE-32 wks, DAZZLE-40 wks, DAZZLE-48 wks, DAZZLE-56 wks |
| LinezolidAlso: ZyvoxLinezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. | Drug | DAZZLE-24 wks, DAZZLE-32 wks, DAZZLE-40 wks, DAZZLE-48 wks, DAZZLE-56 wks |
| LevofloxacinAlso: LevaquinLevoflaxacin is an antibiotic used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, urinary tract infections, chronic prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis. | Drug | DAZZLE-24 wks, DAZZLE-32 wks, DAZZLE-40 wks, DAZZLE-48 wks, DAZZLE-56 wks |
| PyrazinamideAlso: ZinamidePyrazinamide is a medication used in combination with other drugs such as isoniazid and rifampicin in the treatment of Mycobacterium tuberculosis. | Drug | DAZZLE-24 wks, DAZZLE-32 wks, DAZZLE-40 wks, DAZZLE-48 wks, DAZZLE-56 wks |
| WHO MDR-TB regimenAlso: 5-agent treatment regimen for MDR-TBThe WHO guidelines recommend the following 5-agent treatment regimen for MDR-TB: pyrazinamide; a fluoroquinolone; a parenteral agent (typically amikacin or kanamycin); ethionamide (or prothionamide); and either cycloserine or para-aminosalicylic acid, with preference for cycloserine. Short (9 mos) or longer (20-24 mos) treatment schedules can be used. | Drug | WHO MDR-TB regimen- 9 mos or 20-24 mos |
Primary outcome
Successful outcome at 18 months after randomization using culture results, follow up visits,
Time frame: 18 months
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
1 secondary outcome
Secondary - Adverse Events
Time frame: 18 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
C. Robert Horsburgh, MD principal investigator
Boston University
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Delamanid, Linezolid and Levofloxacin in people with Tuberculosis Multi Drug Resistant Active, run by Boston University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Successful outcome at 18 months after randomization using culture results, follow up visits, (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2017.