INSPIRE-CODA: Innovating Shorter, All- Oral, Precised, Individualized Treatment Regimen for Rifampicin Resistant Tuberculosis：Contizolid and Dlamanid Cohort

Sponsor

Beijing Chest Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06081361

Collaborator

(none)

198

Enrollment

Locations

Arms

34.3

Anticipated Duration (Months)

5.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this clinical trial is to compare the efficacy and safety of a Contezolid and Dlamanid-Containing short regimen to standard longer regimen in Rifampicin-resistant pulmonary tuberculosis (RR-TB). The main question[s] it aims to answer are:

Is the efficacy of short regimen better the standard regimen?
Is the short regimen safe enough to replace the standard regimen?

Participants will:

Be given with either short or standard regimen for RR-TB treatment
Be asked to complete the scheduled visit as planned.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Tuberculosis Rifampicin-resistant Tuberculosis	Drug: Bedaquiline Drug: Delamanid Drug: Contezolid Drug: Levofloxacin Drug: Moxifloxacin Drug: Clofazimine Drug: Linezolid Drug: Cycloserine Drug: Prothionamide Drug: Pyrazinamide Drug: Para-Aminosalicylic Acid Drug: Ethambutol	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

198 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Randomized, Open-Label Study To Evaluate The Efficacy And Safety Of A Contezolid And Dlamanid-Containing Short Regimen For The Treatment Of Rifampicin-Resistant Pulmonary Tuberculosis

Anticipated Study Start Date :

Oct 21, 2023

Anticipated Primary Completion Date :

May 31, 2026

Anticipated Study Completion Date :

Aug 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Short-Term Regimen Intervention will be determined based on Fluoroquinolones(FQs) resistance. For those sensitive to FQs: BDQ DLM CZD LFX(MFX) for 6 months For those resistant to FQs: BDQ DLM CZD CFZ for 6 months	Drug: Bedaquiline Oral, 400mg qd for 2 weeks, then 200 mg 3 times per week Other Names: BDQ Drug: Delamanid Oral, 100mg bid Other Names: DLM Drug: Contezolid Oral, 800mg bid Other Names: CZD Drug: Levofloxacin Oral, 400mg qd for weight <50kg, 600-750mg qd for weight ≥50kg Other Names: LFX Drug: Moxifloxacin Oral, 400mg qd Other Names: MFX Drug: Clofazimine Oral, 100mg qd Other Names: CFZ
Active Comparator: Standard Regimen Intervention will be determined based on Fluoroquinolones(FQs) resistance. For those sensitive to FQs: BDQ LZD LFX(MFX) CS CFZ regimen for 6 months, then LFX(MFX) CS CFZ for 12 months For those resistant to FQs: LFX(MFX) will be replaced by Pto, PZA, PAS or EMB	Drug: Bedaquiline Oral, 400mg qd for 2 weeks, then 200 mg 3 times per week Other Names: BDQ Drug: Levofloxacin Oral, 400mg qd for weight <50kg, 600-750mg qd for weight ≥50kg Other Names: LFX Drug: Moxifloxacin Oral, 400mg qd Other Names: MFX Drug: Clofazimine Oral, 100mg qd Other Names: CFZ Drug: Linezolid Oral, 600mg qd Other Names: LZD Drug: Cycloserine Oral, 250mg bid Other Names: CS Drug: Prothionamide Oral, 600mg qd for weight <50kg, 600-800mg qd for weight ≥50kg Other Names: Pto Drug: Pyrazinamide Oral, 1500mg qd for weight <50kg, 1750mg qd for weight ≥50kg Other Names: PZA Drug: Para-Aminosalicylic Acid 8000mg qd for weight <50kg, 10000mg qd for weight ≥50kg Other Names: PAS Drug: Ethambutol 750mg qd for weight <50kg, 1000mg qd for weight ≥50kg Other Names: EMB

Arm

Intervention/Treatment

Experimental: Short-Term Regimen

Intervention will be determined based on Fluoroquinolones(FQs) resistance. For those sensitive to FQs: BDQ DLM CZD LFX(MFX) for 6 months For those resistant to FQs: BDQ DLM CZD CFZ for 6 months

Drug: Bedaquiline

Oral, 400mg qd for 2 weeks, then 200 mg 3 times per week

Other Names:

BDQ

Drug: Delamanid

Oral, 100mg bid

Other Names:

DLM

Drug: Contezolid

Oral, 800mg bid

Other Names:

CZD

Drug: Levofloxacin

Oral, 400mg qd for weight <50kg, 600-750mg qd for weight ≥50kg

Other Names:

LFX

Drug: Moxifloxacin

Oral, 400mg qd

Other Names:

MFX

Drug: Clofazimine

Oral, 100mg qd

Other Names:

CFZ

Active Comparator: Standard Regimen

Intervention will be determined based on Fluoroquinolones(FQs) resistance. For those sensitive to FQs: BDQ LZD LFX(MFX) CS CFZ regimen for 6 months, then LFX(MFX) CS CFZ for 12 months For those resistant to FQs: LFX(MFX) will be replaced by Pto, PZA, PAS or EMB

Drug: Bedaquiline

Oral, 400mg qd for 2 weeks, then 200 mg 3 times per week

Other Names:

BDQ

Drug: Levofloxacin

Oral, 400mg qd for weight <50kg, 600-750mg qd for weight ≥50kg

Other Names:

LFX

Drug: Moxifloxacin

Oral, 400mg qd

Other Names:

MFX

Drug: Clofazimine

Oral, 100mg qd

Other Names:

CFZ

Drug: Linezolid

Oral, 600mg qd

Other Names:

LZD

Drug: Cycloserine

Oral, 250mg bid

Other Names:

Drug: Prothionamide

Oral, 600mg qd for weight <50kg, 600-800mg qd for weight ≥50kg

Other Names:

Pto

Drug: Pyrazinamide

Oral, 1500mg qd for weight <50kg, 1750mg qd for weight ≥50kg

Other Names:

PZA

Drug: Para-Aminosalicylic Acid

8000mg qd for weight <50kg, 10000mg qd for weight ≥50kg

Other Names:

PAS

Drug: Ethambutol

750mg qd for weight <50kg, 1000mg qd for weight ≥50kg

Other Names:

EMB

Outcome Measures

Primary Outcome Measures

Favourable outcome rate at 12 months after treatment completion [Treatment initiation to 12 months after the completion of assigned treatment]
The proportion of participants with a favourable outcome. A participant's outcome will be classified as favourable if their last two sputum culture results are negative unless they have previously been classified as unfavourable. These two cultures must be taken on separate visits (with ≥7d interval); the latest of which being within the month 15-17 from randomization (month 27-29 in the control arm). Participants that don't have a culture result within the time frame because they were unable to produce sputum, will be classified as favourable if their last two cultures are negative and they have not previously been classified as unfavourable.

Secondary Outcome Measures

Unfavourable outcome rate at 12 months after treatment completion [Treatment initiation to 12 months after the completion of assigned treatment]
The proportion of participants with an unfavourable outcome. A participant's outcome will be classified as unfavorable if they: don't have at least one negative sputum culture result at month 15-17 (month 27-29 in control arm) switch treatment because of adverse event / inefectiveness / aquired resistance re-start other anti-TB regimen at anytime during the study prolong treatment over the study regimen discontinue all the assigned drugs for ≥2 months die for any reason during treatment and follow up period
Time to culture conversion [Treatment initiation to 12 months after the completion of assigned treatment]
Time from treatment initiation to first negative result in sputum culture confirmed by two consecutive cultures with an interval of ≥7d
Grade 3 or higher adverse event rate [Treatment initiation to 12 months after the completion of assigned treatment]
Proportion of participants experiencing at least one grade 3 or higher adverse event, or serious adverse event defined by the Division of AIDS severity criteria for adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Newly diagnosed or recurrent rifampicin-resistant tuberculosis confirmed by phenotypic or molecular drug sensitivity test within 60d before screening
Himself/herself (together with his/her guardian for age under 18 years old) willing to participate both study treatment and follow-up, and sign informed consent.

Exclusion Criteria:

Inadequate liver or renal function, history of serious allergic reaction to one or more study drugs, or with other contraindication to study drugs.
Combined extrapulmonary tuberculosis(except for tuberculous pleuritis, endobronchial tuberculosis and tubercular lymphadenitis)
Expected survival ≤3m by investigator
Women in pregnancy or breast feeding period
Used any of the study drugs for more than 2w within 3 months before screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Chest Hospital affiliated to Capital Medical University	Beijing	Beijing	China	101149
2	Hebei Chest Hospital	Shijiazhuang	Hebei	China	050000
3	Harbin Chest Hospital	Harbin	Heilongjiang	China	150000
4	Infectious Disease Hospital of Hulunbuir	Hulunbuir	Inner Mongolia	China
5	Qingdao Chest Hospital	Qingdao	Shandong	China	266000
6	Taiyuan Fourth People's Hospital	Taiyuan	Shanxi	China	030000
7	The 8th Medical Center of Chinese Pla General Hospital	Beijing		China
8	Changsha Central Hospital	Changsha		China
9	Hunan Province Chest Hospital	Changsha		China
10	Chongqing Public Heath Treatment Center	Chongqing		China
11	Dalian Public Health Center	Dalian		China
12	Fuzhou Pulmonary Hospital of Fujian	Fuzhou		China
13	Guangzhou Chest Hospital	Guangzhou		China
14	Heilongjiang Province center for tuberculosis Control and Prevention	Haerbin		China
15	Second Affiliated Hospital of Hainan Medical University	Haikou		China
16	Hangzhou Red Cross Hospital	Hangzhou		China
17	Anhui Chest Hospital	Hefei		China
18	Second People's Hospital of Hohhot	Hohhot		China
19	Jiamusi Infectious Disease Hospital	Jiamusi		China
20	Jiamusi Tumor Hospital	Jiamusi		China
21	Jilin Tuberculosis Hospital	Jilin		China
22	People's Hospital of Linyi	Linyi		China
23	Second Hospital of Nanjing	Nanjing		China
24	Fourth People's Hospital of Nanning	Nanning		China
25	Guangxi Chest Hospital	Nanning		China
26	Shandong public health clinical center	Shandong		China
27	National Medical Center for Infectious Disease	Shanghai		China
28	Affiliated Hospital of Shaoxing University	Shaoxing		China
29	Shenyang Chest Hospital	Shenyang		China
30	Tianjin Haihe Hospital	Tianjin		China
31	Second People's Hospital of Weifang	Weifang		China
32	Wuhan Institute For Tuberculosis Control	Wuhan		China
33	Xi'an Chest Hospital	Xi'an		China
34	First Affiliated Hospital of Xiamen Medical University	Xiamen		China
35	The First Affiliated Hospital of Xinxiang Medical University	Xinxiang		China
36	Henan Provincial Chest Hospital	Zhengzhou		China
37	Affiliated Hospital of Zunyi Medical University	Zunyi		China
38	The 8th Affiliated Hospital of Xinjiang Medical University	Ürümqi		China