Safety and Effectiveness of Delamanid-containing Regimen for MDR-TB Patients in China

• Status: Not yet recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to monitor and evaluate the safety and effectiveness of Delamanid in combination with an optimal background regimen (OBR) of anti-TB drugs for treatment of MDR-TB.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Beijing Chest Hospital

Criteria

Inclusion Criteria:

1. Patients with microbiologically confirmed multidrug-resistant/rifampicin resistant tuberculosis ;

2. Age 18 to 65 years old;

3. MDR-TB treatment has not been started, or treatment has been started but treatment regimen need to be intensified;

4. According to the guidelines of WHO's consolidated guidelines for the treatment of drug-resistant TB and the consensus of Chinese experts in the treatment of multidrug-resistant and rifampicin resistant TB (2019 edition), effective treatment regimens can only be formed by adding Delamanid based on the results of drug susceptibility testing and the previous treatment history;

5. No history of respiratory failure, no history of cardiac dysfunction and clinically significant arrhythmia, QTcF < 450ms;

6. Patients should be able to take medicines and clinical monitoring according to the requirements of the trial during the treatment and follow-up phases, and adverse effects should be reported to the responsible doctor timely ;

7. Patients should sign the informed consent.

Exclusion Criteria:

1. A history of allergy to nitroimidazole and pyrrole drugs such as Delamanid, metronidazole, tinidazole, or any excipient.

2. Serum transaminase increased ≥3 times the upper limit of normal value or total bilirubin increased ≥2.5 times the upper limit of normal, serum albumin <2.8 g / dL, severe renal impairment.

3. Taking strong CYP3A4 inducer drugs (such as carbamazepine).

4. Is known to be pregnant (or planning to become pregnant) .

5. Participants took part in trials of other new unlisted drugs within the past three months;

6. Congenital QT interval prolongation is known or has any disease that may prolong the QT interval or QTc no less than 500 ms;

7. A history of symptomatic arrhythmia or suffering from clinically related bradycardia;

8. Any cardiac disease that can induce arrhythmias, such as severe hypertension, left ventricular hypertrophy (including hypertrophic cardiomyopathy), or congestive heart failure with reduced left ventricular ejection fraction;

9. Electrolyte disturbance, especially hypokalemia, hypocalcemia or hypomagnesemia;

10. Taking drugs known to prolong the QT interval such as the following drugs (but not limited to) :

① Anti-arrhythmic drugs, such as amiodarone, disopyramide, dofetilide, ibutilide, procainamide, quinidine, hydroquinidine, sotalol, etc .;

• Antipsychotic drugs, such as phenothiazine, sertindole, sultopride, chlorpromazine, haloperidol, mesoridazine, pimozide or thioridazine, and antidepressants; ③ Certain antibiotics, including:

• Macrolides, such as erythromycin, clarithromycin, etc ;

• Moxifloxacin, Sparfloxacin;

• Triazole antifungal drugs;

• Spray him with amidine;

• Saquinavir;

④ Some non-sedative antihistamines, such as terfenadine, astemizole, mizolastine, etc.

11. Other drugs with protential cardiac risk : cisapride, haloperidol, domperidone, bepridil, diphemanil, probucol, dimepheptanol, methadone, vinblastine, arsenic trioxide.

Deletion criteria:

1. Those who are found to have exclusion items after enrolled;

2. Serious adverse reactions caused by Delamanid, such as allergic reactions, mental disorders, and liver injury (transaminases increase greater than 3 times the upper limit of normal value or total bilirubin increase greater than 2.5 times the upper limit of normal);

3. QTcF ≥500ms or clinically significant ventricular arrhythmia is confirmed;

4. The expert group made decision that it is not appropriate for the patient to continue the treatment with Delamanid;

5. The patient cannot tolerate the background treatment regimen, or the modified background treatment regimen cannot meet the 3 definitive sensitive drugs or 4 probably sensitive drugs;

6. The patient requests dropout.