Clostridioides Difficile and Frailty

NCT05447533 | Completed

• 1 other identifier: 1106
• Study Type: interventional
• Target: 217
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Frail Elderly; Clostridioides Difficile; Geriatric Assessment; Faecal Microbiota Transplantation; Aged

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Physical functional status

  83-97 weekdays after date of positive PCR test for Clostridioides difficile.

• Overall quality of life assessed by Depression List

  83-97 weekdays after date of positive PCR test for Clostridioides difficile.

• Quality of life assessed by the 5-level EQ-5D Interviewer version

  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

  83-97 weekdays after date of positive PCR test for Clostridioides difficile.

Other Outcomes (5)

• Recurrent Clostridioides difficile infection

  Within period of 90-day follow-up from date of positive PCR test for Clostridioides difficile.

• Time to Faecal microbiota transplantation

  Within period of 90-day follow-up.

• Time to initiation of vancomycin/bactocin treatment

  Within period of 90-day follow-up.

Study Arms (2)

Geriatric tailored assessment and intervention

OTHER

The geriatric tailored intervention consists of the following components: 1. Comprehensive Geriatric Assessment 2. Continued geriatric care during 8 weeks follow-up or until cured.

Other: Comprehensive geriatric assessment (CGA); Other: Continued geriatric care; Other: Faecal microbiota transplantation (FMT)

Standard care

ACTIVE COMPARATOR

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

Interventions

Comprehensive geriatric assessment (CGA) OTHER

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: 1. Severe index, recurrent or refractory CDI as defined by national clinical guidelines or 2. High risk patient according to CGA at first visit. High risk patient is defined frailty grade MPI-2 (moderate) or MPI-3 (severe).

Geriatric tailored assessment and intervention

Continued geriatric care OTHER

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.

Geriatric tailored assessment and intervention

Faecal microbiota transplantation (FMT) OTHER

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.

Geriatric tailored assessment and intervention

Standard care OTHER

Standard care: Patients are not contacted by the geriatric team. They receive usual treatment at the treating physician's discretion.

Standard care

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Patients aged ≥ 70 years and living in the Central Denmark Region
• Positive PCR test Clostridioides difficile

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator
• Horsens Hospital: collaborator
• Randers Regional Hospital: collaborator
• Central Jutland Regional Hospital: collaborator

Study Sites (1)

Department of Geriatrics, Aarhus University Hospital

Aarhus, 8220, Denmark

Location

Related Publications (10)

• Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, Monnet DL, van Dissel JT, Kuijper EJ; ECDIS Study Group. Clostridium difficile infection in Europe: a hospital-based survey. Lancet. 2011 Jan 1;377(9759):63-73. doi: 10.1016/S0140-6736(10)61266-4.

  PMID: 21084111 BACKGROUND

• Czepiel J, Krutova M, Mizrahi A, Khanafer N, Enoch DA, Patyi M, Deptula A, Agodi A, Nuvials X, Pituch H, Wojcik-Bugajska M, Filipczak-Bryniarska I, Brzozowski B, Krzanowski M, Konturek K, Fedewicz M, Michalak M, Monpierre L, Vanhems P, Gouliouris T, Jurczyszyn A, Goldman-Mazur S, Wultanska D, Kuijper EJ, Skupien J, Biesiada G, Garlicki A. Mortality Following Clostridioides difficile Infection in Europe: A Retrospective Multicenter Case-Control Study. Antibiotics (Basel). 2021 Mar 13;10(3):299. doi: 10.3390/antibiotics10030299.

  PMID: 33805755 BACKGROUND

• Cober ED, Malani PN. Clostridium difficile infection in the "oldest" old: clinical outcomes in patients aged 80 and older. J Am Geriatr Soc. 2009 Apr;57(4):659-62. doi: 10.1111/j.1532-5415.2009.02182.x.

  PMID: 19392957 BACKGROUND

• Hensgens MP, Goorhuis A, Dekkers OM, van Benthem BH, Kuijper EJ. All-cause and disease-specific mortality in hospitalized patients with Clostridium difficile infection: a multicenter cohort study. Clin Infect Dis. 2013 Apr;56(8):1108-16. doi: 10.1093/cid/cis1209. Epub 2013 Jan 8.

  PMID: 23300235 BACKGROUND

• Ellis G, Gardner M, Tsiachristas A, Langhorne P, Burke O, Harwood RH, Conroy SP, Kircher T, Somme D, Saltvedt I, Wald H, O'Neill D, Robinson D, Shepperd S. Comprehensive geriatric assessment for older adults admitted to hospital. Cochrane Database Syst Rev. 2017 Sep 12;9(9):CD006211. doi: 10.1002/14651858.CD006211.pub3.

  PMID: 28898390 BACKGROUND

• Gregersen M, Pedersen AB, Damsgaard EM. Comprehensive geriatric assessment increases 30-day survival in the aged acute medical inpatients. Dan Med J. 2012 Jun;59(6):A4442.

  PMID: 22677240 BACKGROUND

• Leibovici-Weissman Y, Atamna A, Schlesinger A, Eliakim-Raz N, Bishara J, Yahav D. Risk factors for short- and long-term mortality in very old patients with Clostridium difficile infection: A retrospective study. Geriatr Gerontol Int. 2017 Oct;17(10):1378-1383. doi: 10.1111/ggi.12866. Epub 2016 Sep 20.

  PMID: 27647625 BACKGROUND

• Jorgensen SMD, Rubak TMM, Damsgaard EM, Dahlerup JF, Hvas CL. Faecal microbiota transplantation as a home therapy to frail older people. Age Ageing. 2020 Oct 23;49(6):1093-1096. doi: 10.1093/ageing/afaa073.

  PMID: 32365381 BACKGROUND

• Hvas CL, Dahl Jorgensen SM, Jorgensen SP, Storgaard M, Lemming L, Hansen MM, Erikstrup C, Dahlerup JF. Fecal Microbiota Transplantation Is Superior to Fidaxomicin for Treatment of Recurrent Clostridium difficile Infection. Gastroenterology. 2019 Apr;156(5):1324-1332.e3. doi: 10.1053/j.gastro.2018.12.019. Epub 2019 Jan 2.

  PMID: 30610862 BACKGROUND

• Rubak T, Baunwall SMD, Gregersen M, Paaske SE, Asferg M, Barat I, Secher-Johnsen J, Riis MG, Rosenbaek JB, Hansen TK, Orum M, Steves CJ, Veilbaek H, Hvas CL, Damsgaard EMS. Early geriatric assessment and management in older patients with Clostridioides difficile infection in Denmark (CLODIfrail): a randomised trial. Lancet Healthy Longev. 2024 Dec;5(12):100648. doi: 10.1016/j.lanhl.2024.100648. Epub 2024 Oct 30.

  PMID: 39488230 DERIVED

MeSH Terms

Interventions

Geriatric Assessment; Fecal Microbiota Transplantation; Standard of Care

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Status; Demography; Population Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Epidemiologic Measurements; Public Health; Environment and Public Health; Biological Therapy; Therapeutics; Quality Indicators, Health Care; Health Services Administration

Study Officials

• Else Marie Damsgaard, Professor

  Department of Geriatrics, Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Functional capacity and Overall Quality of life will be performed on both groups by a trained blinded project assistant during planned visits to the patients. The project assistant will be blinded to randomization status in redcap database.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: June 28, 2022
• First Posted: July 7, 2022
• Study Start: September 16, 2022
• Primary Completion: August 16, 2023
• Study Completion: August 16, 2023
• Last Updated: August 18, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)