Back to resultsA Study of Ultrashort PRS Regimen V in the Treatment of MDR-TB
Primary Purpose
MDR-TB
Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
PRS Regimen V
MDR-TB Treatment Regimen(WHO)
Sponsored by
About this trial
This is an interventional treatment trial for MDR-TB focused on measuring MDR-TB, Delamanid, bedaquiline
Eligibility Criteria
Inclusion Criteria:
- Untreated newly diagnosed patients with rifampicin resistant (RR) or multidrug resistant (MDR)-TB.
- 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.
- Age between 18 and 65.
- No abnormality on EKG.
- Able to understand and sign informed consent form.
Exclusion Criteria:
- Presence of extrapulmonary TB (including tuberculous pleurisy);
- History of allergic reaction to any of the drugs used in the study;
Presence of any of the following conditions that can lead to prolonged QT:
- 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);
- Pathological Q waves (any Q wave duration of > 40 ms or depth > 0.4-0.5 mV);
- Evidence of ventricular pre-excitation (such as Wolff-Parkinson-White Syndrome);
- EKG shows evidence of complete or clinically significant incomplete left or right bundle branch block;
- Evidence of 2nd or 3rd degree heart block;
- Intraventricular conduction delay, QRS durations > 120 ms;
- Slow heart rate, defined as sinus heart rate < 50 bpm;
- Having personal or family history of long QT syndrome;
- Having heart disease, symptomatic or asymptomatic arrhythmia, excluding sinus arrhythmia;
- Fainting (i.e., cardiogenic fainting, not including vasovagal syncope or seizure)
- Having risk factors for Torsade de pointes ventricular tachycardia (e.g. heart failure, hypokalemia, hypomagnesemia)
- Pregnancy or liver, kidney, metabolic, autoimmunity, neurological, psychological or endocrine disease, blood system disease, malignant cancer, long-term users of immunosuppressant drugs.
- Alcoholism
- 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.
- Participating in another clinical trial at the same time.
- History of non-compliance in other clinical trials.
Sites / Locations
- Shanghai Pulmonary HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Group A
Group B(PRS Regimen V)
Arm Description
Treatment according to WHO MDR-TB treatment guidelines (2019).
bedaquiline, delamanid, clofazimine, pyrazinamide
Outcomes
Primary Outcome Measures
patient cure rate
Assessment of cure rate :
Cure.
Treatment completion.
Treatment failure.
Death.
Loss.
Inconclusive.
Treatment success.
Secondary Outcome Measures
Early bactericidal activity (EBA)
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
Time to culture positivity
culture using MGIT 960 and observe the time to detection of positive growth.
Sputum conversion rate
ompare patient sputum conversion rate between the two groups at one month and two months.
Radiology changes
"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.
Relapse rate one and two years after treatment completion.
follow up at 3, 6, 12, 18, and 24 months after treatment completion
Time to Cure by Primary Endpoint criteria
Time to Cure by Primary Endpoint criteria
Full Information
NCT ID
NCT05278988
First Posted
February 24, 2022
Last Updated
August 4, 2022
Sponsor
Shanghai Pulmonary Hospital, Shanghai, China
Collaborators
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
1. Study Identification
Unique Protocol Identification Number
NCT05278988
Brief Title
A Study of Ultrashort PRS Regimen V in the Treatment of MDR-TB
Official Title
A Study of Ultrashort PRS Regimen V in the Treatment of MDR-TB
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2021 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Pulmonary Hospital, Shanghai, China
Collaborators
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
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MDR-TB
Keywords
MDR-TB, Delamanid, bedaquiline
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Active Comparator
Arm Description
Treatment according to WHO MDR-TB treatment guidelines (2019).
Arm Title
Group B(PRS Regimen V)
Arm Type
Experimental
Arm Description
bedaquiline, delamanid, clofazimine, pyrazinamide
Intervention Type
Drug
Intervention Name(s)
PRS Regimen V
Intervention Description
PRS Regimen V(bedaquiline, delamanid, clofazimine, pyrazinamide)
Intervention Type
Drug
Intervention Name(s)
MDR-TB Treatment Regimen(WHO)
Other Intervention Name(s)
WHO Regimen
Intervention Description
Treatment according to WHO MDR-TB treatment guidelines (2019)
Primary Outcome Measure Information:
Title
patient cure rate
Description
Assessment of cure rate :
Cure.
Treatment completion.
Treatment failure.
Death.
Loss.
Inconclusive.
Treatment success.
Time Frame
Through study completion, an average of 18 months
Secondary Outcome Measure Information:
Title
Early bactericidal activity (EBA)
Description
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
Time Frame
treatment initiation (Day 0; D0) and on Day 2 (D2), Day 7 (D7), and Day 14 (D14) after the start of treatment
Title
Time to culture positivity
Description
culture using MGIT 960 and observe the time to detection of positive growth.
Time Frame
Through study completion, an average of 18 months
Title
Sputum conversion rate
Description
ompare patient sputum conversion rate between the two groups at one month and two months.
Time Frame
Through study completion, an average of 18 months
Title
Radiology changes
Description
"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.
Time Frame
Through study completion, an average of 18 months
Title
Relapse rate one and two years after treatment completion.
Description
follow up at 3, 6, 12, 18, and 24 months after treatment completion
Time Frame
At 3, 6, 12, 18, and 24 months
Title
Time to Cure by Primary Endpoint criteria
Description
Time to Cure by Primary Endpoint criteria
Time Frame
6-9 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Untreated newly diagnosed patients with rifampicin resistant (RR) or multidrug resistant (MDR)-TB.
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.
Age between 18 and 65.
No abnormality on EKG.
Able to understand and sign informed consent form.
Exclusion Criteria:
Presence of extrapulmonary TB (including tuberculous pleurisy);
History of allergic reaction to any of the drugs used in the study;
Presence of any of the following conditions that can lead to prolonged QT:
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);
Pathological Q waves (any Q wave duration of > 40 ms or depth > 0.4-0.5 mV);
Evidence of ventricular pre-excitation (such as Wolff-Parkinson-White Syndrome);
EKG shows evidence of complete or clinically significant incomplete left or right bundle branch block;
Evidence of 2nd or 3rd degree heart block;
Intraventricular conduction delay, QRS durations > 120 ms;
Slow heart rate, defined as sinus heart rate < 50 bpm;
Having personal or family history of long QT syndrome;
Having heart disease, symptomatic or asymptomatic arrhythmia, excluding sinus arrhythmia;
Fainting (i.e., cardiogenic fainting, not including vasovagal syncope or seizure)
Having risk factors for Torsade de pointes ventricular tachycardia (e.g. heart failure, hypokalemia, hypomagnesemia)
Pregnancy or liver, kidney, metabolic, autoimmunity, neurological, psychological or endocrine disease, blood system disease, malignant cancer, long-term users of immunosuppressant drugs.
Alcoholism
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.
Participating in another clinical trial at the same time.
History of non-compliance in other clinical trials.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sha wei
Phone
+8602165115006
Ext
2017
Email
13671758200@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Liu yidian
Phone
+8602165115006
Ext
2017
Email
13816676933@139.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sha wei
Organizational Affiliation
Shanghai Pulmonary Hospital, Shanghai, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Pulmonary Hospital
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liu yidian
Phone
+8602165115006
Ext
2017
Email
13816676933@139.com
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
25216831
Citation
Aung KJ, Van Deun A, Declercq E, Sarker MR, Das PK, Hossain MA, Rieder HL. Successful '9-month Bangladesh regimen' for multidrug-resistant tuberculosis among over 500 consecutive patients. Int J Tuberc Lung Dis. 2014 Oct;18(10):1180-7. doi: 10.5588/ijtld.14.0100.
Results Reference
background
PubMed Identifier
20442432
Citation
Van Deun A, Maug AK, Salim MA, Das PK, Sarker MR, Daru P, Rieder HL. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med. 2010 Sep 1;182(5):684-92. doi: 10.1164/rccm.201001-0077OC. Epub 2010 May 4.
Results Reference
background
PubMed Identifier
27035987
Citation
Silva A, Lee BY, Clemens DL, Kee T, Ding X, Ho CM, Horwitz MA. Output-driven feedback system control platform optimizes combinatorial therapy of tuberculosis using a macrophage cell culture model. Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):E2172-9. doi: 10.1073/pnas.1600812113. Epub 2016 Mar 28.
Results Reference
background
Links:
URL
https://apps.who.int/iris/bitstream/handle/10665/311389/9789241550529-eng.pdf?ua=1
Description
WHO consolidated guidelines on drug-resistant tuberculosis treatment
Learn more about this trial
A Study of Ultrashort PRS Regimen V in the Treatment of MDR-TB
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