MDR-TB
Conditions
Keywords
MDR-TB, Delamanid, bedaquiline
Brief summary
This is an exploratory, prospective, randomized, active control, and open label clinical trial to evaluate the efficacy and safety of 6-9 months treatment with the ultrashort PRS Regimen V.
Detailed description
Shortening the course of treatment based on effective therapy can significantly improve patient compliance and reduce the public health burden.Research on optimal drug combination regimens to further shorten the duration and improve the efficacy of multidrug-resistant tuberculosis treatment is an important research direction.The PRS (parabolic response surface, FSC.II) system is an enhanced use of FSC to better identify and optimize optimal drug combinations.In preliminary studies, it was determined that PRS Regimens V （bedaquiline, delamanid, clofazimine, pyrazinamide）was superior to other regimens and would be a promising combination for XDR-TB because it does not contain fluoroquinolones or aminoglycosides. Preliminary trials have demonstrated that this regimen (PRS Regimens IV) can significantly reduce the duration of treatment required for MDR-TB and achieve a relapse-free cure. Therefore, the investigators conducted an exploratory, prospective, randomized, positive-controlled, open, multicenter clinical study of this new regimen to observe the efficacy, safety, and recent relapse rate of the new regimen in the treatment of multidrug-resistant tuberculosis.
Interventions
DRUGPRS Regimen V
PRS Regimen V(bedaquiline, delamanid, clofazimine, pyrazinamide)
DRUGMDR-TB Treatment Regimen(WHO)
Treatment according to WHO MDR-TB treatment guidelines (2019)
Sponsors
Shanghai Public Health Clinical Center
No.85 Hospital, Changning, Shanghai, China
Ganzhou Fifth People's Hospital, China
Weifang Second People's Hospital, China
Anhui Chest Hospital
Fourth Taiyuan People's Hospital, China
Shanghai Pudong New Area Pulmonary Hospital, China
Huashan Hospital
Zhengzhou Sixth People's Hospital, China
Shanghai Pulmonary Hospital, Shanghai, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Untreated newly diagnosed patients with rifampicin resistant (RR) or multidrug resistant (MDR)-TB. 2. Newly treated patients: at least twice confirmed by molecular biology or phenotypic drug susceptibility test to have RR- or MDR-TB; Retreated patients: confirmed once by molecular biology or phenotypic drug susceptibility test to have RR- or MDR-TB. 3. Age between 18 and 65. 4. No abnormality on EKG. 5. Able to understand and sign informed consent form.
Exclusion criteria
1. Presence of extrapulmonary TB (including tuberculous pleurisy); 2. History of allergic reaction to any of the drugs used in the study; 3. Presence of any of the following conditions that can lead to prolonged QT: 1. During screening process, ECG shows QT or QTc interval ≥ 450 ms (permit one non-prescheduled retest within the screening period to re-evaluate the testees' qualification); 2. Pathological Q waves (any Q wave duration of \> 40 ms or depth \> 0.4-0.5 mV); 3. Evidence of ventricular pre-excitation (such as Wolff-Parkinson-White Syndrome); 4. EKG shows evidence of complete or clinically significant incomplete left or right bundle branch block; 5. Evidence of 2nd or 3rd degree heart block; 6. Intraventricular conduction delay, QRS durations \> 120 ms; 7. Slow heart rate, defined as sinus heart rate \< 50 bpm; 8. Having personal or family history of long QT syndrome; 9. Having heart disease, symptomatic or asymptomatic arrhythmia, excluding sinus arrhythmia; 10. Fainting (i.e., cardiogenic fainting, not including vasovagal syncope or seizure) 11. Having risk factors for Torsade de pointes ventricular tachycardia (e.g. heart failure, hypokalemia, hypomagnesemia) 4. Pregnancy or liver, kidney, metabolic, autoimmunity, neurological, psychological or endocrine disease, blood system disease, malignant cancer, long-term users of immunosuppressant drugs. 5. Alcoholism 6. Any patients, based on the judgement of the study medical researchers who are not suitable to participate in the trial or unlikely to complete the trial. 7. Participating in another clinical trial at the same time. 8. History of non-compliance in other clinical trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| patient cure rate | Through study completion, an average of 18 months | Assessment of cure rate : 1. Cure. 2. Treatment completion. 3. Treatment failure. 4. Death. 5. Loss. 6. Inconclusive. 7. Treatment success. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to culture positivity | Through study completion, an average of 18 months | culture using MGIT 960 and observe the time to detection of positive growth. |
| Sputum conversion rate | Through study completion, an average of 18 months | ompare patient sputum conversion rate between the two groups at one month and two months. |
| Early bactericidal activity (EBA) | treatment initiation (Day 0; D0) and on Day 2 (D2), Day 7 (D7), and Day 14 (D14) after the start of treatment | Collect patient sputum between 16:00 to 8:00 the next morning before taking drugs prior to treatment initiation (Day 0; D0) and on Day 2 (D2), Day 7 (D7), and Day 14 (D14) after the start of treatment |
| Relapse rate one and two years after treatment completion. | At 3, 6, 12, 18, and 24 months | follow up at 3, 6, 12, 18, and 24 months after treatment completion |
| Time to Cure by Primary Endpoint criteria | 6-9 month | Time to Cure by Primary Endpoint criteria |
| Radiology changes | Through study completion, an average of 18 months | Significant absorption is defined as lesion absorption ≥ ½. Absorption is defined as lesion absorption ≤ ½. No change if the original lesion has no clear change. Worsened if the original lesion is enlarged or has spread. Closure if the original cavity is enclosed or enclosed by blockage. Shrinkage if diameter of the original cavity decreased by ≥1/2. No change if diameter of the original cavity decreases by \<1/2. Enlarged if diameter of the original cavity increases by \>1/2. |
Countries
China
Outcome results
None listed