A Study of Ultrashort PRS Regimen V in the Treatment of MDR-TB

NCT ID: NCT05278988

Last Updated: 2024-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-01

Study Completion Date

2024-10-30

Brief Summary

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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

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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.

Conditions

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MDR-TB

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group A

Treatment according to WHO MDR-TB treatment guidelines (2019).

Group Type ACTIVE_COMPARATOR

MDR-TB Treatment Regimen(WHO)

Intervention Type DRUG

Treatment according to WHO MDR-TB treatment guidelines (2019)

Group B(PRS Regimen V)

bedaquiline, delamanid, clofazimine, pyrazinamide

Group Type EXPERIMENTAL

PRS Regimen V

Intervention Type DRUG

PRS Regimen V(bedaquiline, delamanid, clofazimine, pyrazinamide)

Interventions

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PRS Regimen V

PRS Regimen V(bedaquiline, delamanid, clofazimine, pyrazinamide)

Intervention Type DRUG

MDR-TB Treatment Regimen(WHO)

Treatment according to WHO MDR-TB treatment guidelines (2019)

Intervention Type DRUG

Other Intervention Names

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WHO Regimen

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shanghai Public Health Clinical Center

OTHER_GOV

Sponsor Role collaborator

No.85 Hospital, Changning, Shanghai, China

OTHER

Sponsor Role collaborator

Ganzhou Fifth People's Hospital, China

UNKNOWN

Sponsor Role collaborator

Weifang Second People's Hospital, China

UNKNOWN

Sponsor Role collaborator

Anhui Chest Hospital

OTHER

Sponsor Role collaborator

Fourth Taiyuan People's Hospital, China

UNKNOWN

Sponsor Role collaborator

Shanghai Pudong New Area Pulmonary Hospital, China

UNKNOWN

Sponsor Role collaborator

Huashan Hospital

OTHER

Sponsor Role collaborator

Zhengzhou Sixth People's Hospital, China

UNKNOWN

Sponsor Role collaborator

Shanghai Pulmonary Hospital, Shanghai, China

OTHER

Sponsor Role lead

Responsible Party

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Wei Sha MD & PhD

Director, Head of Tuberculosis Department,Shanghai Pulmonary Hospital, Principal Investigator, Clinical Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sha wei

Role: PRINCIPAL_INVESTIGATOR

Shanghai Pulmonary Hospital, Shanghai, China

Locations

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Shanghai Pulmonary Hospital

Shanghai, , China

Site Status

Countries

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China

References

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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.

Reference Type BACKGROUND
PMID: 25216831 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20442432 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27035987 (View on PubMed)

Related Links

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https://apps.who.int/iris/bitstream/handle/10665/311389/9789241550529-eng.pdf?ua=1

WHO consolidated guidelines on drug-resistant tuberculosis treatment

Other Identifiers

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K21-024

Identifier Type: -

Identifier Source: org_study_id