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This is a prospective, open-label, single-arm study to explore the safety and the efficacy of CMTS0929 for patients with Clostridioides difficile infection (CDI).
At least 12 subjects who meet all the inclusion criteria but do not meet any exclusion criteria will be enrolled in this study. Data of demographic characteristics and clinical data will be collected. After treatment, they will enter the follow-up period for safety and efficacy evaluation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental | Eligible subjects will receive treatment with CMTS0929. They will be administered one unit of the liquid via colonic transendoscopic enteral tube (cTET) for three consecutive days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CMTS0929 | Biological | CMTS0929 is defined as suspension from washed microbiota. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The safety of CMTS0929 | The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0: The severity of AE was graded as mild (grade 1), moderate (grade 2), severe/disabling (grade 3), life threatening (grade 4), and death (grade 5). All AE were divided in definitely, probably and possibly related to treatment. The treatment-related AE we focused on included microbiota-related AEs (e.g., infection, diarrhea, abdominal pain, etc.) and route of delivery related AEs (e.g., nausea, vomiting, etc.) | Four-week |
| Measure | Description | Time Frame |
|---|---|---|
| The safety of CMTS0929 | The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0: The severity of AE was graded as mild (grade 1), moderate (grade 2), severe/disabling (grade 3), life threatening (grade 4), and death (grade 5). All AE were divided in definitely, probably and possibly related to treatment. The treatment-related AE we focused on included microbiota-related AEs (e.g., infection, diarrhea, abdominal pain, etc.) and route of delivery related AEs (e.g., nausea, vomiting, etc.) |
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Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to enter the study:
Exclusion Criteria:
Subjects meeting any of the following exclusion criteria must be excluded from the study:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Faming Zhang, PhD | Contact | 086-025-58509883 | fzhang@njmu.edu.cn | |
| Bota Cui, MD | Contact | 086-025-58509884 | cuibota@njmu.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Faming Zhang, PhD | The Second Hospital of Nanjing Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University | Nanjing | Jiangsu | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27025836 | Background | Millan B, Park H, Hotte N, Mathieu O, Burguiere P, Tompkins TA, Kao D, Madsen KL. Fecal Microbial Transplants Reduce Antibiotic-resistant Genes in Patients With Recurrent Clostridium difficile Infection. Clin Infect Dis. 2016 Jun 15;62(12):1479-1486. doi: 10.1093/cid/ciw185. Epub 2016 Mar 29. | |
| 23323867 | Background |
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| ID | Term |
|---|---|
| D003015 | Clostridium Infections |
| ID | Term |
|---|---|
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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Eligible subjects will receive treatment with CMTS0929. They will be administered one unit of the liquid via colonic transendoscopic enteral tube (cTET) for three consecutive days.
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| Immediately, One-week, Two-week, Eight-week, Twenty four-week |
| The complete response rate of CDI-related diarrhea | Having no diarrhea for at least two consecutive days (with normal stool consistency (Bristol Stool Form Scale score ≤ 5) and 1-2 bowel movements per day). | Four-week, Eight-week |
| The ultra-early complete response rate of CDI-related diarrhea | Having no diarrhea for at least two consecutive days (with normal stool consistency (Bristol Stool Form Scale score ≤ 5) and 1-2 bowel movements per day). | One-week post treatment |
| The early complete response rate of CDI-related diarrhea | Having no diarrhea for at least two consecutive days (with normal stool consistency (Bristol Stool Form Scale score ≤ 5) and 1-2 bowel movements per day). | Two-week post treatment |
| The non-response rate of CDI-related diarrhea | Having at least 3 bowel movements per day for at least two consecutive days and the stools are unformed (Bristol Stool Form Scale score of 6-7), and further anti-CDI treatment is required. | Two-week, Four-week, Six-week, Eight-week post treatment |
| The recurrence rate of CDI-related diarrhea | After the disappearance of CDI-related diarrhea, the recurrence of CDI-related diarrhea occurs, and the detection of Clostridioides difficile toxins is positive (judged by glutamate dehydrogenase [GDH] and enzyme immunoassays [EIAs]). | Four-week, Six-week, Eight-week, Twenty four-week |
| The major disease progression rate of CDI | Progression to severe CDI (SCDI)/severe complicated CDI (ScCDI) (defined as high fever ≥ 38.5°C, white blood cell count > 15×10⁹/L, increased serum creatinine [> 50% higher than the baseline level], hypotension, septic shock, increased serum lactate [> 2.2 mmol/L], intestinal obstruction, toxic megacolon, intestinal perforation, or any fulminant course [i.e., the patient's condition deteriorates rapidly, or requires treatment in the intensive care unit (ICU), or is complicated by organ failure]), death, emergency colectomy, receiving ≥ 2 courses of fecal microbiota transplantation (FMT)/washed microbiota transplantation (WMT) or other forms of approved or investigational salvage therapy, or early withdrawal from the study or loss to follow-up) | Twenty four-week |
| The salvage/replacement treatment rate of CDI | The salvage/replacement treatments include receiving approved or investigational anti-infective treatment, toxin-neutralizing treatment, other FMT/WMT outside the protocol, and emergency, hospitalization, ICU or surgical treatment due to CDI-related diarrhea, etc. | Immediately, One-week, Two-week, Four-week, Eight-week, Twenty four-week |
| van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16. |
| 31611298 | Background | Ng SC, Kamm MA, Yeoh YK, Chan PKS, Zuo T, Tang W, Sood A, Andoh A, Ohmiya N, Zhou Y, Ooi CJ, Mahachai V, Wu CY, Zhang F, Sugano K, Chan FKL. Scientific frontiers in faecal microbiota transplantation: joint document of Asia-Pacific Association of Gastroenterology (APAGE) and Asia-Pacific Society for Digestive Endoscopy (APSDE). Gut. 2020 Jan;69(1):83-91. doi: 10.1136/gutjnl-2019-319407. Epub 2019 Oct 14. |
| 31563878 | Background | Cammarota G, Ianiro G, Kelly CR, Mullish BH, Allegretti JR, Kassam Z, Putignani L, Fischer M, Keller JJ, Costello SP, Sokol H, Kump P, Satokari R, Kahn SA, Kao D, Arkkila P, Kuijper EJ, Vehreschild MJG, Pintus C, Lopetuso L, Masucci L, Scaldaferri F, Terveer EM, Nieuwdorp M, Lopez-Sanroman A, Kupcinskas J, Hart A, Tilg H, Gasbarrini A. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice. Gut. 2019 Dec;68(12):2111-2121. doi: 10.1136/gutjnl-2019-319548. Epub 2019 Sep 28. |
| 33175698 | Background | Ademe M. Benefits of fecal microbiota transplantation: A comprehensive review. J Infect Dev Ctries. 2020 Oct 31;14(10):1074-1080. doi: 10.3855/jidc.12780. |
| 25938992 | Background | Drekonja D, Reich J, Gezahegn S, Greer N, Shaukat A, MacDonald R, Rutks I, Wilt TJ. Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review. Ann Intern Med. 2015 May 5;162(9):630-8. doi: 10.7326/M14-2693. |
| 34003176 | Background | Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, Stollman NH. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol. 2021 Jun 1;116(6):1124-1147. doi: 10.14309/ajg.0000000000001278. |
| 33326565 | Background | Pike CM, Theriot CM. Mechanisms of Colonization Resistance Against Clostridioides difficile. J Infect Dis. 2021 Jun 16;223(12 Suppl 2):S194-S200. doi: 10.1093/infdis/jiaa408. |
| 23804381 | Background | Antharam VC, Li EC, Ishmael A, Sharma A, Mai V, Rand KH, Wang GP. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol. 2013 Sep;51(9):2884-92. doi: 10.1128/JCM.00845-13. Epub 2013 Jun 26. |
| 32242357 | Background | Guh AY, Mu Y, Winston LG, Johnston H, Olson D, Farley MM, Wilson LE, Holzbauer SM, Phipps EC, Dumyati GK, Beldavs ZG, Kainer MA, Karlsson M, Gerding DN, McDonald LC; Emerging Infections Program Clostridioides difficile Infection Working Group. Trends in U.S. Burden of Clostridioides difficile Infection and Outcomes. N Engl J Med. 2020 Apr 2;382(14):1320-1330. doi: 10.1056/NEJMoa1910215. |