Clinical trial NCT05278988: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: MDR-TB
Keywords: MDR-TB
Delamanid
bedaquiline
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
Collaborators: name: Shanghai Public Health Clinical Center
name: No.85 Hospital, Changning, Shanghai, China
name: Ganzhou Fifth People's Hospital, China
name: Weifang Second People's Hospital, China
name: Anhui Chest Hospital
name: Fourth Taiyuan People's Hospital, China
name: Shanghai Pudong New Area Pulmonary Hospital, China
name: Huashan Hospital
name: Zhengzhou Sixth People's Hospital, China
First posted: 2022-03-15
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: patient cure rate
timeFrame: Through study completion, an average of 18 months
Secondary outcomes:
measure: Early bactericidal activity (EBA)
timeFrame: treatment initiation (Day 0; D0) and on Day 2 (D2), Day 7 (D7), and Day 14 (D14) after the start of treatment
measure: Time to culture positivity
timeFrame: Through study completion, an average of 18 months
measure: Sputum conversion rate
timeFrame: Through study completion, an average of 18 months
measure: Radiology changes
timeFrame: Through study completion, an average of 18 months
measure: Relapse rate one and two years after treatment completion.
timeFrame: At 3, 6, 12, 18, and 24 months
measure: Time to Cure by Primary Endpoint criteria
timeFrame: 6-9 month
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
Study officials:
affiliation: Shanghai Pulmonary Hospital, Shanghai, China
name: Sha wei
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.