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

NCT ID: NCT04421495

Last Updated: 2022-07-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 608 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-16
• Study Completion Date: 2024-07-16

Brief 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.

Detailed Description

This is a single-arm, multicenter, phase #, open-label trial to evaluate the safety and effectiveness of delamanid-containing regimen in men and women aged 18 to 65 years with microbiologically confirmed pulmonary MDR-TB in China. A target of 600 participants will be enrolled. The study will consist of a screening phase of up to 8 weeks, an open-label study treatment phase of 13-20 months, and a follow-up phase of 12-month after end of study treatment. During the study treatment phase, participants will receive an MDR-TB regimen consisting of 24 weeks of delamanid in combination with 13-20 months of a background regimen.

Participants will be instructed to take their assigned dose of delamanid with at least 3 additional probably effective background drugs according to national and international guidelines. Delamanid dosage will be 100 mg twice daily (b.i.d.) for 24 weeks.

Safety evaluations will include monitoring of AEs, visual acuity testing, routine blood examinations (such as hematology, clinical chemistry, HIV, TSH [for subjects receiving PTO] measurements), urinalysis, and electrocardiograms (ECGs). Participants will initiate treatment with the study regimen if they meet the study eligibility criteria.The end of study will be considered as the last contact for the last participant in the study.

A participant will be considered to have completed the study if he or she has completed the 13-20 months study treatment phase and the required post-treatment follow-up phase. Participants who prematurely discontinue study treatment (unless they withdraw consent) will be followed up for 12 months after end of delamanid treatment.

Conditions

Multidrug Resistant Tuberculosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

delamanid containing regimen arm

the only one arm to be studied with delamid-containing regimen.

Group Type: EXPERIMENTAL

Delamanid

Intervention Type: DRUG

the eligible patients will be give damanid-containing regimen

Interventions

Delamanid

the eligible patients will be give damanid-containing regimen

Intervention Type: DRUG

Other Intervention Names

anti-TB new drug containing regimen

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Chest Hospital

OTHER

Sponsor Role: lead

Responsible Party

Liang Li

Vice president

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Liang Li

Role: PRINCIPAL_INVESTIGATOR

Beijing Chest Hospital

Locations

Beijing Chest Hospital, Capital Medical University

Beijing, , China

Changsha Central Hospital

Changsha, , China

Public Health Clinical Center of Chengdu

Chengdu, , China

Chongqing Infectious Disease Medical Center

Chongqing, , China

Fuzhou Pulmonary Hospital of Fujian

Fuzhou, , China

Guangzhou Chest Hospital

Guangzhou, , China

Guiyang Public Health Clinical Center

Guiyang, , China

Heilongjiang Province center for tuberculosis Control and Prevention

Haerbin, , China

Hangzhou Red Cross Hospital

Hangzhou, , China

Jiamusi Tumor Hospital

Jiamusi, , China

Tuberculosis Hospital in Jilin Province

Jilin, , China

Shandong Provincial Chest Hospital

Jinan, , China

The Third People's Hospital of Kunming City

Kunming, , China

Lanzhou Pulmonary Hospital

Lanzhou, , China

Longtan Hospital of Guangxi Zhuang Autonomous Region

Liuzhou, , China

Jiangxi Chest (Third People) Hospital

Nanchang, , China

Shanghai Pulmonary Hospital

Shanghai, , China

Hebei Chest Hospital

Shijiangzhuang, , China

The Fifth People Hospital of Suzhou

Suzhou, , China

The Fourth People's Hospital of Taiyuan

Taiyuan, , China

Wuhan Institute For Tuberculosis Control

Wuhan, , China

Wuhan Jinyintan Hospital

Wuhan, , China

Shanxi Provincial Tuberculosis Institute

Xi'an, , China

Xi'an Chest Hospital

Xi'an, , China

Henan Provincial Chest Hospital

Zhengzhou, , China

Countries

China

References

Yang F, Yin M, Jiang X, Zhao X, An X, Liu Y, Yuan Y. Delamanid-containing regimens over 24 weeks for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis: preliminary results from a single center in a multicenter, prospective, observational study. Front Med (Lausanne). 2025 Sep 29;12:1631030. doi: 10.3389/fmed.2025.1631030. eCollection 2025.

Reference Type: DERIVED

PMID: 41090140 (View on PubMed)

Other Identifiers

LCSY-TB-2020-002

Identifier Type: -

Identifier Source: org_study_id