Fecal Transplantation for Primary Clostridium Difficile Infection (COLONIZE)
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|ClinicalTrials.gov Identifier: NCT03796650|
Recruitment Status : Recruiting
First Posted : January 8, 2019
Last Update Posted : July 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Clostridium Difficile Infection||Other: Fecal microbiota transplantation Drug: Vancomycin||Phase 3|
Up to one third of patients with clostridium difficile infection treated with antibiotics experience recurrent or relapsing symptoms within a few weeks. Even with subsequent antibiotic treatment, multiple recurrences/relapses are frequent. Fecal microbiota transplantation (FMT) has been shown to be significantly more effective in curing recurrent CDI than repeated antibiotic treatment. In current guidelines, FMT is proposed as a treatment option after multiple recurrences/relapses of CDI. The rationale to reserve transplantation of donor feces for recurrent and difficult cases of CDI is a possible risk of pathogen transmittance and the process of finding a donor and screen for communicable disease.
The effect of FMT for recurrent CDI, however, suggests that this therapy may be more effective than antibiotics in inducing a durable cure also for primary CDI. If the therapeutic effect of FMT proves to be equal (non-inferior) or more effective than antibiotics, FMT may be the preferable treatment option due to favourable ecological impact compared to antibiotics. In an era with increasing concerns about overuse of antibiotics and emergence of antibiotic resistant bacteria, it is important to investigate therapeutic alternatives that may reduce the need for antibiotics.
This trial is a phase III multicentre, randomized controlled, open-label non-inferiority parallel group trial with two arms (FMT and antibiotics), and is a continuation of the phase II trial IMT for Primary Clostridium Difficile Infection (NCT02301000). In the current trial, patients with Clostridium difficile infection and no previous CDI within 12 months prior to inclusion will be randomized 1:1 to FMT or 10 days of guideline-recommended antibiotic therapy (vancomycin 125 mg four times a day).
Patients are recruited in Norwegian hospitals.
The investigators plan to use frozen microbiota, because supply is easier to organize, compared to fresh fecal samples. Patients in the FMT treatment group will receive one rectal dose of FMT, originating from screened, healthy donors. Patients who are not cured by the first dose is offered a protocol defined additional FMT treatment. In the case of clinical deterioration, appropriate measures will be undertaken according to current guidelines.
Patient treatment outcomes are evaluated after 14, 60 and 365 days from inclusion and treatment initiation.
An interim analysis is planned after inclusion of the first 94 patients (corresponding to 50% of the planned number of patients).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||188 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Randomized clinical trial with two parallel treatment arms with a 1:1 allocation.|
|Masking:||None (Open Label)|
|Masking Description:||An open-label, partly assessor blinded trial.|
|Official Title:||COmparative Effectiveness of intestinaL microbiOta Versus vaNcomycin for Primary c. Difficile Infection - randomiZEd Trials|
|Actual Study Start Date :||July 17, 2019|
|Estimated Primary Completion Date :||January 31, 2024|
|Estimated Study Completion Date :||January 31, 2024|
Experimental: Fecal microbiota transplantation
Fecal microbiota from healthy, screened stool donors at the University Hospital of North Norway. Patients will receive one FMT enema immediately after enrolment.
Other: Fecal microbiota transplantation
50 g donor feces suspended in saline with added glycerol, administered by a enema kit.
Active Comparator: Antibiotic treatment
Patients randomized to the control group will receive a ten-day course of oral vancomycin four times a day. This is according to international guidelines for primary C. difficile treatment.
Peroral vancomycin 125 mg q.i.d. for ten days.
- Patients with durable cure [ Time Frame: 60 days ]Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, with the assigned treatment alone.
- Patients with durable cure with additional treatment. [ Time Frame: 60 days ]Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, with or without the need of additional treatment (FMT, metronidazole or vancomycin).
- Treatment adverse events [ Time Frame: 60 and 365 days ]Proportion of patients with adverse events.
- Patients with long-time cure [ Time Frame: 365 days ]Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, and without recurrent C. difficile infection within 365 days after treatment start.
- Health-economic evaluation [ Time Frame: 365 days ]Health-economic analysis of the two compared treatment modalities
- Fecal composition and treatment outcome [ Time Frame: 60 days ]
Correlation in fecal composition changes before versus after treatment, and treatment outcome (such as bacterial diversity and fecal short chain fatty acids).
Subgroup analyses will be performed for sex, age, co-morbidities, and FMT donor.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03796650
|Contact: Kjetil Garborg, MD, PhDfirstname.lastname@example.org|
|Contact: Frederik Emil Juul, MDemail@example.com|
|Vestre Viken HF, Bærum Hospital||Not yet recruiting|
|Sandvika, Gjettum, Norway, 1346|
|Contact: Øystein Rose, MD|
|Haukeland universitetssykehus||Not yet recruiting|
|Contact: Trygve Hausken, MD, PhD|
|Sykehuset Østfold Kalnes||Not yet recruiting|
|Contact: Jon Birger Haug, MD, PhD|
|UNN Harstad||Not yet recruiting|
|Contact: Peter H. Johnsen, MD|
|Sørlandet Hospital HF||Not yet recruiting|
|Contact: Håvard Wiig, MD|
|Sub-Investigator: Rita Helleren, MD|
|Sykehuset Levanger||Not yet recruiting|
|Contact: Eivind Ness-Jensen, MD, PhD|
|Lovisenberg sykehus||Not yet recruiting|
|Contact: Jørgen Valeur, MD|
|Oslo University Hospital Rikshospitalet||Recruiting|
|Contact: Frederik Emil Juul, MD firstname.lastname@example.org|
|Contact: Siv Elisabeth Isaksen|
|Principal Investigator: Kjetil Garborg, MD, PhD|
|Oslo University Hospital Ullevål||Recruiting|
|Contact: Kristian Tonby, MD, PhD|
|Sub-Investigator: Frederik Emil Juul, MD|
|Telemark Hospital HF||Not yet recruiting|
|Contact: Hilde Skudal, MD|
|UNN Tromsø||Not yet recruiting|
|Contact: Rasmus Goll, MD|
|Sykehuset i Vestfold||Not yet recruiting|
|Contact: Birgitte Seip, MD|
|Ålesund Sjukehus||Not yet recruiting|
|Contact: Dag Arne Lihaug Hoff, MD|
|Study Chair:||Michael Bretthauer, MD, PhD||Oslo Universitetssykehus HF, Rikshospitalet|