Clostridioides Difficile and Frailty

Study Overview
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Brief Summary
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CDI is a major cause of antibiotics-associated diarrhoea. More than half of the patients affected are 70 years or older and frail. Mortality among older patients with CDI is high. Faecal microbiota transplantation (FMT) is a life-saving therapy which reduce symptom duration and mortality. The FMT procedure usually requires hospital attendance, and frail old patients often are too weak to tolerate transportation to hospital and may therefore be withheld treatment. The overall aim of the present project is to investigate whether a multimodal geriatric assessment, treatment and follow-up of frail older patients with CDI can improve patient survival compared with standard care. In particular, it is explored whether an expanded collaboration between the geriatric wards, early clinical assessment and home treatment with FMT contribute to increased patient survival rates.

Detailed Description
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This is a multi-centre randomised clinical trial that test two established care pathways in the assessment and treatment of old patients with Clostridioides difficile infection (CDI). We aim to include 216 patients aged 70 years or older with Clostridioides difficile infection. Patients are randomised in a 1:1 ratio to either geriatric tailored intervention or standard care as defined by national clinical guidelines. The primary outcome is 90-day survival.

Official Title
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Frail Old Patients With Clostridioides Difficile Infection: Improvement of Quality in Treatment and Care

Conditions
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Frail Elderly, Clostridioides Difficile, Geriatric Assessment, Faecal Microbiota Transplantation, Aged

Intervention / Treatment
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* Other: Comprehensive geriatric assessment (CGA)
* Other: Continued geriatric care
* Other: Faecal microbiota transplantation (FMT)
* Other: Standard care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 70 years and living in the Central Denmark Region Positive PCR test Clostridioides difficile Exclusion Criteria: Previously included > 4 episodes of CDI FMT treatment 8 weeks before date of positive PCR test for Clostridioides difficile. End of life care defined as follows: end of life care treatment has been initiated before positive PCR test for CDI and the patient has days/few weeks of survival (investigator consensus based on review of electronic medical journal (EMR)) Patients already received Comprehensive Geriatric Assessment, defined as follows: when diagnosed with CDI affiliated with the Department of Geriatrics (in- or outpatient activity).

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel-group randomised clinical trial (RCT). The study compares two well-known organisations of care and does not involve experimental treatments or sampling of biological material outside of routine care. It is therefore classified as a quality improvement project by the Central Denmark Region Committees on Health Research Ethics (case number 1-10-72-1-21).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Geriatric tailored assessment and intervention<br>The geriatric tailored intervention consists of the following components: Comprehensive Geriatric Assessment Continued geriatric care during 8 weeks follow-up or until cured. | Other: Comprehensive geriatric assessment (CGA)<br>* Within 5 weekdays from date of randomization (not included) a standardized CGA with a tailor-made intervention will be performed in the allocated ward or at home by a geriatric team. Bedside Multidimensional Prognostic Index (MPI) will be performed. A geriatric Clostridioides difficile infection checklist will be performed by local geriatrician and secure an early assessment of CDI and treatment strategy. When indication: pre-treatment with vancomycin 125 mg x 4. Routine biochemical analyses for patients with Clostridioides difficile infection. Evaluation of indication for faecal microbiota transplantation (FMT). Criteria for FMT rely on the geriatric assessment and will be considered for the patient if the patient fulfil one of the following: Severe index, recurrent or refractory CDI as defined by national clinical guidelines or High risk patient according to CGA at first visit. High risk patient is defined frailty grade MPI-2 (moderate) or MPI-3 (severe).<br>Other: Continued geriatric care<br>* Continued specialized geriatric care through 8 weeks of follow-up. Minimum of follow-up is 8 weeks from last FMT or start of vancomycin/fidaxomicin treatment. Tailormade telephone contacts and/or visits in case of clinical exacerbation. Performed by local geriatric teams. The geriatric department remains responsible for the CDI during 8 weeks of follow-up or until cured.<br>Other: Faecal microbiota transplantation (FMT)<br>* When clinical indication for FMT, this will be delivered as 15-25 capsules (  50 grams of donor faeces from one thoroughly screened healthy donor). If the patient is not admitted to hospital, FMT will be de-livered as home treatment via regional geriatric team or project manager and project nurse. If the patient has dysphagia diagnosed by dysphagia screening or carries a nasogastric tube, vancomycin and FMT can be delivered by naso-jejunal tube (Bengmark 10 Fr, Nutricia), requiring a referral to the Radiology department for verification of duodenal/jejunal tube placement. If available in the specific department, placement can be controlled via mobile x-ray.<br>|
| Active Comparator: Standard care<br>Standard care: Patients are not contacted by the geriatric team. They receive usual treatment at the treating physician's discretion. Standard care of Clostridioides difficile infection in Denmark is described in the National clinical guideline. | Other: Standard care<br>* Standard care: Patients are not contacted by the geriatric team. They receive usual treatment at the treating physician's discretion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-day mortality | Mortality within 90 days from date of positive Polymerase Chain Reaction (PCR) test for Clostridioides difficile (CD). Date of death will be collected from the electronic medical journals according to date of death registration. | Date of 90-day follow-up will include day of positive PCR test for CD and day 90 from date of positive PCR test for CD. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical functional status | Functional Recovery Score (FRS). Sum-score, range 100-0 (100 is the highest physical functional status score possible, 0 is the lowest). FRS will be performed on both groups by a blinded and trained project assessor during planned visits to the patients at 90-days follow-up. FRS will be performed according to the functional capacity at 90-day of follow-up as well as a retrospective FRS assessment according to functional capacity on the date of positive PCR test for Clostridioides difficile. This will be performed by asking the patient/relatives about the functional capacity. FRS will be performed within 83-97 weekdays after date of positive PCR test for Clostridioides difficile. | 83-97 weekdays after date of positive PCR test for Clostridioides difficile. | 
| Overall quality of life assessed by Depression List | The Overall quality of life will be assessed by the Overall Quality of Life Depression List (OQoL-DL) and will be performed on both groups by a blinded and trained project assessor during planned visits to the patients at 90-days follow-up within 83-97 weekdays after date of positive PCR test for Clostridioides difficile. | 83-97 weekdays after date of positive PCR test for Clostridioides difficile. | 
| Quality of life assessed by the 5-level EQ-5D Interviewer version | The quality of life will be assessed by the 5-level EQ-5D version (EQ-5D-5L). The EQ-5D-5L be performed on both groups by a blinded and trained project assessor during planned visits to the patients at 90-days follow-up within 83-97 weekdays after date of positive PCR test for Clostridioides difficile. | 83-97 weekdays after date of positive PCR test for Clostridioides difficile. | 
| Quality of life assessed by the 5-level EQ-5D proxy 2 version | The quality of life will be assessed by the 5-level EQ-5D proxy 2 version (EQ-5D-5L). The EQ-5D-5L proxy 2 version be performed in both groups by proxy invited online. The significant others (proxy) will receive the survey at 90-days follow-up within 83-97 weekdays after date of positive PCR test for Clostridioides difficile. | 83-97 weekdays after date of positive PCR test for Clostridioides difficile. |