Clostridioides Difficile InfectionDONATENCT05709184
Lyophilized Fecal Microbiome Transfer vs. Vancomycin Monotherapy for Primary Clostridioides Difficile Infection
A study testing Lyophilized fecal microbiome transfer and Vancomycin in people with Clostridioides Difficile Infection, run by Rambam Health Care Campus at 6 sites in 6 countries.
Trial summary
The goal of this clinical trial is to test whether lyophilized fecal microbime transfer - a dried extract of bacteria from the stool of healthy donors - is better than antibiotic therapy only for treating primary clostridioides difficile infection (CDI) in adult participants. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridioides Difficile Infection
- What is being tested?
- Lyophilized fecal microbiome transfer and Vancomycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 196 participants
- Where
- 6 sitesin 6 countries
- Study dates
- 15 Nov 2023to Mar 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Consenting adults ≥18 years old with non-fulminant primary CDI.
- Both non-severe and severe patients will be included.
- Primary CDI (pCDI) will be defined as the patient's first event of CDI in the past 6 months: New-onset diarrhea (≥3 unformed bowel movements (UBM) per day for more than 24 hours) and laboratory detection of toxigenic C. difficile in feces.
- A positive CD stool sample will be defined per study center according to international guidelines, with an obligatory positive toxin test to assure the presence of an active toxigenic CD strain.
Who cannot join
- Patients who cannot provide informed consent and do not have a legal guardian;
- History of CDI 6 months prior to screening
- Known presence of other stool pathogens known to cause diarrhea;
- Patients who cannot swallow;
- Background diagnosis of inflammatory bowel disease, irritable bowel syndrome (IBS), or any other chronic diarrheal disorder;
- Active gastrointestinal graft versus host disease (GVHD);
Show all 19Show fewer
- Neutropenia <500/ml3;
- Food allergy leading to anaphylaxis;
- Prior total colectomy or the presence of a small intestinal stoma;
- Perforated intestine or intestinal fistula or major abdominal surgery in the last 30 days;
- Fulminant or life-threatening CDI defined as the occurrence of ileus, septic shock or toxic megacolon. Signs of fulminant disease are: white blood cell count >30,000 cells/mL; temperature >40°C; evidence of hypotension [systolic blood pressure <90 mmHg], peritoneal signs, and significant dehydration;
- Early fulminant CDI (ICU patients) defined as patients showing progression despite treatment with a sequential organ failure assessment score (SOFA score) ≥ 4 due to CDI (13) at day 2 of treatment (prior to randomization);
- Patients who receive systemic antibiotics due to other reasons which cannot be stopped until 1 day prior to randomization (day 2 of antibiotic therapy);
- Patients that were not recruited to the study by day 4 of CDI therapy will be excluded from participation;
- Patients with <3 months life expectancy;
- Inability or unwillingness to comply with the study protocol, including ingesting capsules, and providing blood or stool samples as scheduled;
- Participation in another interventional study;
- In the opinion of the investigator, inappropriateness for the trial (eg, patients with known hypersensitivity to vancomycin);
- Pregnancy and breastfeeding.
Trial locations and contacts
6 sites in 6 countries.
6 sites in 6 countries
Canada1 site, 1 recruiting
- Recruiting
University of Alberta
Edmonton
Dina Kao, Prof., 780-719-0598, dkao@ualberta.ca
Hungary1 site, 1 recruiting
- Not yet recruiting
University of Debrecen
Debrecen
Gergely Nagy, 0036 20 419-7188, ngergely@hotmail.com
Israel1 site, 1 recruiting
- Recruiting
Rambam Health Care Campus
Haifa
Milena Pitashny, MD, 972-4-7771108, m_pitashny@rmc.gov.il
Inbar Kesten, PhD, 972-4-7771578, i_kesten@rmc.gov.il
Italy1 site, 1 recruiting
- Not yet recruiting
Gemelly institute Policlinico Universitario Fondazione Agostino Gemelli
Rome
Gianluca Ianiro, Prof., 39 338 192 9859, gianluca.ianiro@unicatt.it
Lithuania1 site, 1 recruiting
- Not yet recruiting
Hospital of Lithuania University of Health Sciences Kauno klinikos
Kaunas
Juozas Kupcinskas, MD, 370-639-51045, Juozas.Kupcinskas@lsmuni.lt
United Kingdom1 site, 1 recruiting
- Not yet recruiting
Imperial College of London
London
Benjamin Mullish, MD PhD, 7576478561, b.mullish@imperial.ac.uk
About this study
Official title: Lyophilized Fecal Microbiome Transfer for Primary Clostridioides Difficile Infection (DONATE Study): a Multicenter Randomized Controlled Trial
The goal of this clinical trial is to test whether lyophilized fecal microbime transfer - a dried extract of bacteria from the stool of healthy donors - is better than antibiotic therapy only for treating primary clostridioides difficile infection (CDI) in adult participants.
The main question it aims to answer is whether lyophilized fecal microbiome transfer lowers the number of episodes of CDI compared to antibiotic therapy.
Read more
Participants will be assigned to one of two groups:
- In the intervention group participants will be given vancomycin by mouth for five days followed by 5 days of capsules of lyophilized fecal microbiome to swallow, up until day 10.
- In the control group participants will be given vancomycin by mouth for ten days.
- All participants will be asked to arrive for two follow-up visits and to fill out questionnaires. In addition, all participants will be asked to give stool samples before antibiotic therapy and on the two follow-up visits.
Researchers will compare the intervention group and the control group to see if there is a difference in symptoms degree after ten days and in recurrence of the infection after two months. They will also compare side effects, the total use of antibiotics and the change in the composition of bacteria in the stool, namely the presence of bacteria that are resistant to many drugs.
Read the detailed description
This is a multicenter, transnational randomized controlled trial comparing a short course of vancomycin therapy followed by oral lyophilized fecal microbiome transfer (Lyo-FMT) capsules (intervention group) with standard vancomycin monotherapy (control group), for adults with primary Clostridioides difficile infection (pCDI).
The target population will be adult patients with non-fulminant pCDI in the community/hospital according to the setting at the recruiting center. pCDI will be defined as the patient's first event of CDI in the last 6 months presenting with a new-onset diarrhea (≥3 unformed bowel movements per day for more than 24 hours) and laboratory detection of toxigenic C. difficile in feces. A positive C. difficile stool sample will be defined per study center according to international guidelines, with an obligatory positive toxin test to assure the presence of an active toxigenic CD strain. Both non-severe and severe patients will be included.
Consenting patients will be randomly assigned to one of two treatment modalities: vancomycin followed by oral lyophilized FMT capsules (intervention group) or vancomycin monotherapy group.
- Lyo-FMT group (intervention group) - vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 5 days (day 1 - initiation of antibiotic therapy by the clinical team), followed by a loading dose of oral lyophilized FMT capsules on day 6 (15 capsules). On days 7-10, patients will receive 10 Lyo-FMT capsules per day. A total of 55 capsules, derived from ~30-40g of the original material, will be administered throughout 5 days. Prior to each FMT administration, patients will be asked to fast for 8 hours. Bowel preparation or proton pump inhibitor use will not be required per protocol. The loading dose will be administered under medical supervision, while further dosing can be administered at the patient's home/institute, after training and guidance.
- Antibiotic monotherapy group (control group) - vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 10 days (day 1 - initiation of therapy by the clinical team, not from randomization).
If symptoms persist on day 10 from the initiation of therapy, further treatment will be given according to study group allocation. In the Lyo-FMT group, FMT will be repeated in the form of 15 FMT capsules per course as clinically indicated. If no resolution of symptoms will be documented after 2 days of FMT, the same FMT course (15 capsules) will be repeated, up to 3 times. For patients in the antibiotic monotherapy group, an extension of the vancomycin treatment with the same doses will be given for 7 more days. Laboratory testing for the presence of C. difficile will not be required for the administration of repeated treatment, but will be annotated if performed. If symptoms will persist beyond day 18 of the study in both groups (8 days after the end of first treatment), we will allow treatment according to clinical judgement at the local study center. Patients will be free to decide if they want to stop their participation in the study at all times. Persistent symptoms beyond day 20 of the study will be considered as a clinical failure for the purposes of secondary outcome analysis. At any point, if there is a deterioration of the patient towards fulminant disease, clinical judgement will prevail as per protocol for fulminant cases.
During the study period and across study centers, we will encourage clinicians to use vancomycin as empiric treatment for pCDI. However, according to local clinical practice, patients may receive an antibiotic other than vancomycin (e.g. metronidazole). In both study groups, patients that were treated with another antibiotic agent in the first 24 hours, will be switched to vancomycin prior to day 3 of the study. The day of initiation of therapy will be considered from the first day of any antibiotic therapy that was administered. Randomization will be done within 72 hours from the initiation of any therapy for CDI.
In both groups, if a patient receives concurrent systemic antibiotics for other indications, the research team will contact the clinical team to understand if these antibiotics can be safely stopped 24 hours prior to randomization (day 3 from initiation of therapy). If systemic antibiotics cannot be stopped, then the patient will be excluded from the study.
In case of a CDI recurrence, the patient will be considered as reaching the primary outcome. We will permit treatment of CDI recurrences according to clinical judgement. We will provide Lyo-FMT for the treatment of recurrent CDI If available at the study center and required by the clinical team. In case of the development of fulminant disease, we will allow any therapy judged by the clinical team as appropriate. All cases with fulminant disease will be assessed by a surgical team for a timely fashioned colectomy if indicated. The development of fulminant disease from day 8 of the study onwards (3 days on FMT treatment) will be considered as clinical failure for the purposes of secondary outcome analysis.
The trial's primary efficacy outcome is the recurrence of CDI by week 8. Recurrence will be defined as the re-appearance of CDI symptoms (at least 3 unformed bowel movements per day for at least 2 days) with positive C. difficile stool test more than 3 days after the resolution of symptoms and requiring anti-CDI treatment. The primary outcome will be assessed by an observer blinded to study group assignment.
- Conditions
- Clostridioides Difficile Infection
- Being tested
- Lyophilized fecal microbiome transfer, Vancomycin
- Keywords
- Gut microbiome, Colonization resistance, Fecal microbiome transfer, Lyophilization, Multi-drug resistant organisms, Clostridioides Difficile Infection
- Medical subject headings
- Clostridium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lyophilized fecal microbiome transferCombination product
Also called FMT
Five days of vancomycin followed by five days of lyophilized fecal microbiome transfer, administered in a loading dose of 15 capsules, and a daily maintenance dose of 10 capsules.
VancomycinDrug
Also called CDI antibiotic treatment
Ten days of oral vancomycin 125 mg four times daily
| Study group | Role | What they receive |
|---|---|---|
| Lyophilized fecal microbiome transfer (Lyo-FMT) | Experimental | Vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 5 days (day 1 - initiation of therapy by the clinical team), followed by a loading dose of oral Lyo-FMT capsules on day 6 (15 capsules). On days 7-10, patients will receive 10 Lyo-FMT capsules per day. A total of 55 capsules, derived from ~30-40g of the original material, will be administered throughout 5 days. Prior to each Lyo-FMT administration, patients will be asked to fast for 8 hours. Bowel preparation or proton pump inhibitor use will not be required per protocol. The loading dose will be administered under medical supervision, while further dosing can be administered at the patient's home/institute, after training and guidance Receives: Combination Product: Lyophilized fecal microbiome transfer |
| Vancomycin monotherapy | Active comparator | Vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 10 days (day 1 - initiation of therapy by the clinical team, not from randomization). Receives: Drug: Vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
CDI recurrence
The re-appearance of CDI symptoms (at least 3 unformed bowel movements per day for at least 2 days) with positive CD stool test more than 3 days after the resolution of symptoms and requiring anti-CDI treatment
Measured: 8 weeks
Secondary outcomes (6)
Clinical cure
Cessation of CDI related symptoms by day 10 of the study with no further symptoms/conditions (persistent symptoms, fulminant disease, death and colectomy) needing additional therapy
Measured: 10 days
CDI recurrence in patients who achieved clinical cure
CDI recurrence in patients who achieved clinical cure at day 10
Measured: 8 weeks
Sustained clinical response
Cessation of CDI related symptoms by day 10 of the study with no further symptoms/conditions (persistent symptoms, fulminant disease, death, colectomy and recurrence) needing additional therapy
Measured: 8 weeks
Serious adverse events
Mortality, bacteremia attributable to FMT, and hospitalization due to CDI during study period
Measured: 8 weeks
Patient reported outcomes (PROs) and preferences
The C. difficile health-related quality of life (HRQOL) questionnaire,13 EuroQol 5 Dimensions 5 Level (EQ-5D-5L),14 and Work Productivity and Activity Impairment (WPAI) Questionnaire15 will be administered at screening visit and again at week 2, and week 8. The C difficile HRQOL questionnaire is specifically developed and validated to assess patients with CDI. Although EQ-5D-5L and WPAI are not specifically designed for patients with CDI, they are well validated instruments and have been used in clinical research across a variety of conditions and health status. If follow-up visits are deemed non-essential and are conducted by phone, these questionnaires may be emailed out or mailed out to patients based on patient preference and to be returned to the study sites.
Measured: At baseline and 8 weeks
Patient preference for treatment
A patient preference questionnaire designed by the investigators
Measured: At baseline and week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2023
- Study start15 Nov 2023
- Primary completionNov 2025 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Clostridioides Difficile InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 196 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Collaborators
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, European Institute of Oncology, University of Alberta, Imperial College London, University of Debrecen, Lithuanian University of Health Sciences
- Responsible party
- Principal investigator, Milena Pitashny, MD, Rambam Health Care Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05709184
- Sponsor's protocol ID
- RMB-0176-22
- Acronym
- DONATE
- Status last verified
- Apr 2024
- First submitted
- 24 Jan 2023
- Last updated
- 10 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lawson PA, Citron DM, Tyrrell KL, Finegold SM. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O'Toole 1935) Prevot 1938. Anaerobe. 2016 Aug;40:95-9. doi: 10.1016/j.anaerobe.2016.06.008. Epub 2016 Jun 28.
PubMed 27370902Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, Holzbauer SM, Meek JI, Phipps EC, Wilson LE, Winston LG, Cohen JA, Limbago BM, Fridkin SK, Gerding DN, McDonald LC. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Feb 26;372(9):825-34. doi: 10.1056/NEJMoa1408913.
PubMed 25714160Lewis BB, Buffie CG, Carter RA, Leiner I, Toussaint NC, Miller LC, Gobourne A, Ling L, Pamer EG. Loss of Microbiota-Mediated Colonization Resistance to Clostridium difficile Infection With Oral Vancomycin Compared With Metronidazole. J Infect Dis. 2015 Nov 15;212(10):1656-65. doi: 10.1093/infdis/jiv256. Epub 2015 Apr 28.
PubMed 25920320Rewers M, Hyoty H, Lernmark A, Hagopian W, She JX, Schatz D, Ziegler AG, Toppari J, Akolkar B, Krischer J; TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY) Study: 2018 Update. Curr Diab Rep. 2018 Oct 23;18(12):136. doi: 10.1007/s11892-018-1113-2.
PubMed 30353256van 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.
PubMed 23323867Adler A, Miller-Roll T, Bradenstein R, Block C, Mendelson B, Parizade M, Paitan Y, Schwartz D, Peled N, Carmeli Y, Schwaber MJ. A national survey of the molecular epidemiology of Clostridium difficile in Israel: the dissemination of the ribotype 027 strain with reduced susceptibility to vancomycin and metronidazole. Diagn Microbiol Infect Dis. 2015 Sep;83(1):21-4. doi: 10.1016/j.diagmicrobio.2015.05.015. Epub 2015 Jun 3.
PubMed 26116225Huttner BD, de Lastours V, Wassenberg M, Maharshak N, Mauris A, Galperine T, Zanichelli V, Kapel N, Bellanger A, Olearo F, Duval X, Armand-Lefevre L, Carmeli Y, Bonten M, Fantin B, Harbarth S; R-Gnosis WP3 study group. A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial. Clin Microbiol Infect. 2019 Jul;25(7):830-838. doi: 10.1016/j.cmi.2018.12.009. Epub 2019 Jan 4.
PubMed 30616014Juul FE, Garborg K, Bretthauer M, Skudal H, Oines MN, Wiig H, Rose O, Seip B, Lamont JT, Midtvedt T, Valeur J, Kalager M, Holme O, Helsingen L, Loberg M, Adami HO. Fecal Microbiota Transplantation for Primary Clostridium difficile Infection. N Engl J Med. 2018 Jun 28;378(26):2535-2536. doi: 10.1056/NEJMc1803103. Epub 2018 Jun 2. No abstract available.
PubMed 29860912Camacho-Ortiz A, Gutierrez-Delgado EM, Garcia-Mazcorro JF, Mendoza-Olazaran S, Martinez-Melendez A, Palau-Davila L, Baines SD, Maldonado-Garza H, Garza-Gonzalez E. Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome. PLoS One. 2017 Dec 20;12(12):e0189768. doi: 10.1371/journal.pone.0189768. eCollection 2017.
PubMed 29261736Kao D, Roach B, Silva M, Beck P, Rioux K, Kaplan GG, Chang HJ, Coward S, Goodman KJ, Xu H, Madsen K, Mason A, Wong GK, Jovel J, Patterson J, Louie T. Effect of Oral Capsule- vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA. 2017 Nov 28;318(20):1985-1993. doi: 10.1001/jama.2017.17077.
PubMed 29183074Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875.
PubMed 25322359Cammarota 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.
PubMed 31563878Staley C, Hamilton MJ, Vaughn BP, Graiziger CT, Newman KM, Kabage AJ, Sadowsky MJ, Khoruts A. Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study. Am J Gastroenterol. 2017 Jun;112(6):940-947. doi: 10.1038/ajg.2017.6. Epub 2017 Feb 14.
PubMed 28195180Reigadas E, Bouza E, Olmedo M, Vazquez-Cuesta S, Villar-Gomara L, Alcala L, Marin M, Rodriguez-Fernandez S, Valerio M, Munoz P. Faecal microbiota transplantation for recurrent Clostridioides difficile infection: experience with lyophilized oral capsules. J Hosp Infect. 2020 Jun;105(2):319-324. doi: 10.1016/j.jhin.2019.12.022. Epub 2019 Dec 26.
PubMed 31883938Haifer C, Paramsothy S, Borody TJ, Clancy A, Leong RW, Kaakoush NO. Long-Term Bacterial and Fungal Dynamics following Oral Lyophilized Fecal Microbiota Transplantation in Clostridioides difficile Infection. mSystems. 2021 Feb 2;6(1):e00905-20. doi: 10.1128/mSystems.00905-20.
PubMed 33531405
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lyophilized Fecal Microbiome Transfer for Primary Clostridioides Difficile Infection (DONATE Study): a Multicenter Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05709184
- Acronym / sponsor ID
- DONATE / RMB-0176-22
- Conditions
- Clostridioides Difficile Infection
- Keywords
- Gut microbiome, Colonization resistance, Fecal microbiome transfer, Lyophilization, Multi-drug resistant organisms, Clostridioides Difficile Infection
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 196 participants (estimated)
- Lead sponsor
- Rambam Health Care CampusUniversity, hospital or other
- Collaborators
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, European Institute of Oncology, University of Alberta, Imperial College London, University of Debrecen, Lithuanian University of Health Sciences
- Study start
- 15 Nov 2023 (actual)
- Primary completion
- Nov 2025 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 2 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to test whether lyophilized fecal microbime transfer - a dried extract of bacteria from the stool of healthy donors - is better than antibiotic therapy only for treating primary clostridioides difficile infection (CDI) in adult participants.
The main question it aims to answer is whether lyophilized fecal microbiome transfer lowers the number of episodes of CDI compared to antibiotic therapy.
Participants will be assigned to one of two groups:
- In the intervention group participants will be given vancomycin by mouth for five days followed by 5 days of capsules of lyophilized fecal microbiome to swallow, up until day 10.
- In the control group participants will be given vancomycin by mouth for ten days.
- All participants will be asked to arrive for two follow-up visits and to fill out questionnaires. In addition, all participants will be asked to give stool samples before antibiotic therapy and on the two follow-up visits.
Researchers will compare the intervention group and the control group to see if there is a difference in symptoms degree after ten days and in recurrence of the infection after two months. They will also compare side effects, the total use of antibiotics and the change in the composition of bacteria in the stool, namely the presence of bacteria that are resistant to many drugs.
Detailed description
This is a multicenter, transnational randomized controlled trial comparing a short course of vancomycin therapy followed by oral lyophilized fecal microbiome transfer (Lyo-FMT) capsules (intervention group) with standard vancomycin monotherapy (control group), for adults with primary Clostridioides difficile infection (pCDI).
The target population will be adult patients with non-fulminant pCDI in the community/hospital according to the setting at the recruiting center. pCDI will be defined as the patient's first event of CDI in the last 6 months presenting with a new-onset diarrhea (≥3 unformed bowel movements per day for more than 24 hours) and laboratory detection of toxigenic C. difficile in feces. A positive C. difficile stool sample will be defined per study center according to international guidelines, with an obligatory positive toxin test to assure the presence of an active toxigenic CD strain. Both non-severe and severe patients will be included.
Consenting patients will be randomly assigned to one of two treatment modalities: vancomycin followed by oral lyophilized FMT capsules (intervention group) or vancomycin monotherapy group.
- Lyo-FMT group (intervention group) - vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 5 days (day 1 - initiation of antibiotic therapy by the clinical team), followed by a loading dose of oral lyophilized FMT capsules on day 6 (15 capsules). On days 7-10, patients will receive 10 Lyo-FMT capsules per day. A total of 55 capsules, derived from ~30-40g of the original material, will be administered throughout 5 days. Prior to each FMT administration, patients will be asked to fast for 8 hours. Bowel preparation or proton pump inhibitor use will not be required per protocol. The loading dose will be administered under medical supervision, while further dosing can be administered at the patient's home/institute, after training and guidance.
- Antibiotic monotherapy group (control group) - vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 10 days (day 1 - initiation of therapy by the clinical team, not from randomization).
If symptoms persist on day 10 from the initiation of therapy, further treatment will be given according to study group allocation. In the Lyo-FMT group, FMT will be repeated in the form of 15 FMT capsules per course as clinically indicated. If no resolution of symptoms will be documented after 2 days of FMT, the same FMT course (15 capsules) will be repeated, up to 3 times. For patients in the antibiotic monotherapy group, an extension of the vancomycin treatment with the same doses will be given for 7 more days. Laboratory testing for the presence of C. difficile will not be required for the administration of repeated treatment, but will be annotated if performed. If symptoms will persist beyond day 18 of the study in both groups (8 days after the end of first treatment), we will allow treatment according to clinical judgement at the local study center. Patients will be free to decide if they want to stop their participation in the study at all times. Persistent symptoms beyond day 20 of the study will be considered as a clinical failure for the purposes of secondary outcome analysis. At any point, if there is a deterioration of the patient towards fulminant disease, clinical judgement will prevail as per protocol for fulminant cases.
During the study period and across study centers, we will encourage clinicians to use vancomycin as empiric treatment for pCDI. However, according to local clinical practice, patients may receive an antibiotic other than vancomycin (e.g. metronidazole). In both study groups, patients that were treated with another antibiotic agent in the first 24 hours, will be switched to vancomycin prior to day 3 of the study. The day of initiation of therapy will be considered from the first day of any antibiotic therapy that was administered. Randomization will be done within 72 hours from the initiation of any therapy for CDI.
In both groups, if a patient receives concurrent systemic antibiotics for other indications, the research team will contact the clinical team to understand if these antibiotics can be safely stopped 24 hours prior to randomization (day 3 from initiation of therapy). If systemic antibiotics cannot be stopped, then the patient will be excluded from the study.
In case of a CDI recurrence, the patient will be considered as reaching the primary outcome. We will permit treatment of CDI recurrences according to clinical judgement. We will provide Lyo-FMT for the treatment of recurrent CDI If available at the study center and required by the clinical team. In case of the development of fulminant disease, we will allow any therapy judged by the clinical team as appropriate. All cases with fulminant disease will be assessed by a surgical team for a timely fashioned colectomy if indicated. The development of fulminant disease from day 8 of the study onwards (3 days on FMT treatment) will be considered as clinical failure for the purposes of secondary outcome analysis.
The trial's primary efficacy outcome is the recurrence of CDI by week 8. Recurrence will be defined as the re-appearance of CDI symptoms (at least 3 unformed bowel movements per day for at least 2 days) with positive C. difficile stool test more than 3 days after the resolution of symptoms and requiring anti-CDI treatment. The primary outcome will be assessed by an observer blinded to study group assignment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lyophilized fecal microbiome transfer (Lyo-FMT) | Experimental | Combination Product: Lyophilized fecal microbiome transferVancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 5 days (day 1 - initiation of therapy by the clinical team), followed by a loading dose of oral Lyo-FMT capsules on day 6 (15 capsules). On days 7-10, patients will receive 10 Lyo-FMT capsules per day. A total of 55 capsules, derived from ~30-40g of the original material, will be administered throughout 5 days. Prior to each Lyo-FMT administration, patients will be asked to fast for 8 hours. Bowel preparation or proton pump inhibitor use will not be required per protocol. The loading dose will be administered under medical supervision, while further dosing can be administered at the patient's home/institute, after training and guidance |
| Vancomycin monotherapy | Active comparator | Drug: VancomycinVancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 10 days (day 1 - initiation of therapy by the clinical team, not from randomization). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Consenting adults ≥18 years old with non-fulminant primary CDI.
- Both non-severe and severe patients will be included.
- Primary CDI (pCDI) will be defined as the patient's first event of CDI in the past 6 months: New-onset diarrhea (≥3 unformed bowel movements (UBM) per day for more than 24 hours) and laboratory detection of toxigenic C. difficile in feces.
- A positive CD stool sample will be defined per study center according to international guidelines, with an obligatory positive toxin test to assure the presence of an active toxigenic CD strain.
Key exclusion criteria (19 listed)
- Patients who cannot provide informed consent and do not have a legal guardian;
- History of CDI 6 months prior to screening
- Known presence of other stool pathogens known to cause diarrhea;
- Patients who cannot swallow;
- Background diagnosis of inflammatory bowel disease, irritable bowel syndrome (IBS), or any other chronic diarrheal disorder;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lyophilized fecal microbiome transferAlso: FMTFive days of vancomycin followed by five days of lyophilized fecal microbiome transfer, administered in a loading dose of 15 capsules, and a daily maintenance dose of 10 capsules. | Combination product | Lyophilized fecal microbiome transfer (Lyo-FMT) |
| VancomycinAlso: CDI antibiotic treatmentTen days of oral vancomycin 125 mg four times daily | Drug | Vancomycin monotherapy |
Primary outcome
CDI recurrence
Time frame: 8 weeks
The re-appearance of CDI symptoms (at least 3 unformed bowel movements per day for at least 2 days) with positive CD stool test more than 3 days after the resolution of symptoms and requiring anti-CDI treatment
6 secondary outcomes
Clinical cure
Time frame: 10 days
CDI recurrence in patients who achieved clinical cure
Time frame: 8 weeks
Sustained clinical response
Time frame: 8 weeks
Serious adverse events
Time frame: 8 weeks
Patient reported outcomes (PROs) and preferences
Time frame: At baseline and 8 weeks
Patient preference for treatment
Time frame: At baseline and week 8
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2024.
- Background: PubMed 27370902Lawson PA, Citron DM, Tyrrell KL, Finegold SM. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O'Toole 1935) Prevot 1938. Anaerobe. 2016 Aug;40:95-9. doi: 10.1016/j.anaerobe.2016.06.008. Epub 2016 Jun 28.
- Background: PubMed 25714160Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, Holzbauer SM, Meek JI, Phipps EC, Wilson LE, Winston LG, Cohen JA, Limbago BM, Fridkin SK, Gerding DN, McDonald LC. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Feb 26;372(9):825-34. doi: 10.1056/NEJMoa1408913.
- Background: PubMed 25920320Lewis BB, Buffie CG, Carter RA, Leiner I, Toussaint NC, Miller LC, Gobourne A, Ling L, Pamer EG. Loss of Microbiota-Mediated Colonization Resistance to Clostridium difficile Infection With Oral Vancomycin Compared With Metronidazole. J Infect Dis. 2015 Nov 15;212(10):1656-65. doi: 10.1093/infdis/jiv256. Epub 2015 Apr 28.
- Background: PubMed 30353256Rewers M, Hyoty H, Lernmark A, Hagopian W, She JX, Schatz D, Ziegler AG, Toppari J, Akolkar B, Krischer J; TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY) Study: 2018 Update. Curr Diab Rep. 2018 Oct 23;18(12):136. doi: 10.1007/s11892-018-1113-2.
- Background: PubMed 23323867van 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.
- Background: PubMed 26116225Adler A, Miller-Roll T, Bradenstein R, Block C, Mendelson B, Parizade M, Paitan Y, Schwartz D, Peled N, Carmeli Y, Schwaber MJ. A national survey of the molecular epidemiology of Clostridium difficile in Israel: the dissemination of the ribotype 027 strain with reduced susceptibility to vancomycin and metronidazole. Diagn Microbiol Infect Dis. 2015 Sep;83(1):21-4. doi: 10.1016/j.diagmicrobio.2015.05.015. Epub 2015 Jun 3.
- Background: PubMed 30616014Huttner BD, de Lastours V, Wassenberg M, Maharshak N, Mauris A, Galperine T, Zanichelli V, Kapel N, Bellanger A, Olearo F, Duval X, Armand-Lefevre L, Carmeli Y, Bonten M, Fantin B, Harbarth S; R-Gnosis WP3 study group. A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial. Clin Microbiol Infect. 2019 Jul;25(7):830-838. doi: 10.1016/j.cmi.2018.12.009. Epub 2019 Jan 4.
- Background: PubMed 29860912Juul FE, Garborg K, Bretthauer M, Skudal H, Oines MN, Wiig H, Rose O, Seip B, Lamont JT, Midtvedt T, Valeur J, Kalager M, Holme O, Helsingen L, Loberg M, Adami HO. Fecal Microbiota Transplantation for Primary Clostridium difficile Infection. N Engl J Med. 2018 Jun 28;378(26):2535-2536. doi: 10.1056/NEJMc1803103. Epub 2018 Jun 2. No abstract available.
- Background: PubMed 29261736Camacho-Ortiz A, Gutierrez-Delgado EM, Garcia-Mazcorro JF, Mendoza-Olazaran S, Martinez-Melendez A, Palau-Davila L, Baines SD, Maldonado-Garza H, Garza-Gonzalez E. Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome. PLoS One. 2017 Dec 20;12(12):e0189768. doi: 10.1371/journal.pone.0189768. eCollection 2017.
- Background: PubMed 29183074Kao D, Roach B, Silva M, Beck P, Rioux K, Kaplan GG, Chang HJ, Coward S, Goodman KJ, Xu H, Madsen K, Mason A, Wong GK, Jovel J, Patterson J, Louie T. Effect of Oral Capsule- vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA. 2017 Nov 28;318(20):1985-1993. doi: 10.1001/jama.2017.17077.
- Background: PubMed 25322359Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875.
- Background: PubMed 31563878Cammarota 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
6 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lyophilized fecal microbiome transfer and Vancomycin in people with Clostridioides Difficile Infection, run by Rambam Health Care Campus at 6 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada, Hungary, Israel, Italy, Lithuania and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Milena Pitashny, MD (972-4-7771108, m_pitashny@rmc.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CDI recurrence (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05709184, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2024.