Clostridium Difficile Infection (CDI) in Hematologic Patients.

Incidence, Clinical Characteristics, Strain Characterization, Treatment and Outcome of Clostridium Difficile Infection (CDI) in Hematologic Patients

The microbiology department prospectively generates a data base of all episodes of Clostridium difficile infection (CDI) in the institution, the investigators will analyse the evolution of the episodes and the incidence per 10,000 days of stay of cases of diagnosed CDI in the Hematological wards and the rest of the hospital during the 2006-2018 period. The investigators will also compare the impact on haematological paediatric population.

In order to analyse the clinical and epidemiological characteristics of CDI in this population, a case and control study will be conducted, reviewing the medical records of patients who have had an episode of diarrhoea caused by C. difficile in an hematological unit, which will be compared with non-hematological patients who have had an CDI episode These patients will be selected randomly from the Microbiology Department database. The sample size will be 400 patients, 200 per arm. The histories will be reviewed according to a pre-established clinical protocol including epidemiological, clinical, therapeutic and evolution variables.

A prospective study in 2019-2020 will also be conducted. The investigators will include all patients diagnosed with an hematological/oncological disease or with any immunosuppressive condition, who have a positive detection of toxigenic Clostridium difficile. Patients will be followed for at least 2 months. For each patient a protocol data will be filled prospectively.

Study Overview

• Status: Unknown
• Conditions: C.Difficile Diarrhea
• Intervention / Treatment: Other: No intervention

Detailed Description

A retrospective case control study (2006-2018) and a prospective study 2019-2020.

Study subjects

All patients diagnosed with a hematological disease who had a detection of toxigenic Clostridium difficile in the laboratory within the 2006-2018 period will be included in the study. Hematological patients with a negative Clostridium difficile infection (CDI) test in the same period will be included as controls, For controls, out of the number of cases within that study period, 200 will be randomly selected with the aid of the Excel software, with the tools randomization (RAND) and INDEX to ensure there is no bias. For each patient a protocol data will be filled retrospectively including the variables listed below.

Additionally, a prospective study in 2019-2020 will also be conducted. We will include all patients diagnosed with an hematological/oncological disease or with any immunosuppressive condition, who have a positive detection of toxigenic Clostridium difficile. Patients will be followed for at least 2 months. For each patient a protocol data will be filled prospectively including the variables listed below.

For all the study period 2006-2018 a total of approximately 200 patients will be included.

For the prospective study 2019-2020 approximately 50 patients will be included.Data collection

For the last 15 years, the institution has kept a prospective record of all episodes of CDI diagnosed in the hospital. This record enables the investigators to assess incidence, incidence density.

The data collected will include age, sex, hospital department or outpatient clinic diagnosis of CDI. Data regarding the underlying conditions and comorbidity factors, clinical data regarding the CDI episode days of diarrhea, presence of abdominal pain, abdominal distention, fever, hypotension, toxic megacolon, pseudomembranous colitis, and severity of the CDI episode according to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) criteria. Analytical data on the day of diagnosis will be recorded. Treatment data will be recorded. Outcome will also recorded be recorded: need for intensive care unit (ICU) admission, need for surgery for CDI episode, recurrence, mortality, and CDI-associated mortality (For more details please find attached the clinical protocol).

The investigators will also assess all the changes regarding different procedures, management and treatments that have occurred during the study period, including all changes in the diagnostic procedures.

From January 2003 to February 2011, diagnosis of CDI was performed on all stool specimens for which a clinical request for C. difficile testing was made. From March 2011 to current days, diagnosis of CDI was also performed in all unformed stool specimens regardless of clinical request.

Laboratory procedure All C. difficile strains will be characterized at molecular level including ribotype, as it is the most widespread method for the molecular typing of Clostridium difficile. It is based on the detection of polymorphisms located in the intergenic region between genes 16S and 23S RNA by polymerase chain reaction (PCR) and electrophoresis on high resolution agarose gels and will be performed according to the technique described by Stubss et al.[13]The resulting ribotyping profiles will be compared to those of international libraries. Additionally antimicrobial susceptibility testing will be performed on these strains.

All analyses will be performed using SPSS 18.0 (SPSS Inc, Chicago, Illinois, USA). Qualitative variables will appear with their frequency distribution. Quantitative variables will be expressed as the median and interquartile range (IQR). Groups will be compared using the Fisher exact test for categorical variables and the t test or Mann-Whitney test for continuous variables. A multivariate logistic regression model will be used to assess predictors of poor outcome of CDI. The odds ratio (OR) and 95% confidence interval (CI) were calculated. A p value <0.05 will be considered significant.

Based on data from our center, for the retrospective part of the study, the total number of hematological patients with CDI corresponding to the study period is approximately 200 patients, all of them will be studied, the sample size for controls will be of 200 patients (ratio 1:1).

For the prospective study, also based in data from our center, approximately 50 patients will be enrolled.

• Study Type: Observational
• Enrollment (Anticipated): 450

Contacts and Locations

• Study Contact: Name: Elena Reigadas, PharmD, PhD; Phone Number: +34915868453; Email: elena.reigadas@salud.madrid.org
• Study Contact Backup: Name: Emilio Bouza, MD,PhD

Study Locations

• Spain
  • Madrid, Spain, 28007
    • Recruiting
    • Hgu Gregorio Maranon
    • Contact: Elena Reigadas, PhD; Phone Number: +34915868453; Email: elena.reigadas@salud.madrid.org
    • Contact: Emilio Bouza, MDPhD; Phone Number: +34915868453; Email: emilio.bouza@gmail.com
    • Principal Investigator: Elena Reigadas, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Based on data from our center, for the retrospective part of the study, the total number of hematological patients with CDI corresponding to the study period is approximately 200 patients, all of them will be studied, the sample size for controls will be of 200 patients (ratio 1:1).

For the prospective study, also based in data from our center, approximately 50 patients will be enrolled.

Description

Inclusion Criteria:

• All patients diagnosed with a hematological disease who had a detection of toxigenic Clostridium difficile in the laboratory within the 2006-2018 period will be included in the study. Hematological patients with a negative CDI test in the same period will be included as controls.
• All patients diagnosed with an hematological/oncological disease or with any immunosuppressive condition, who have a positive detection of toxigenic Clostridium difficile in 2019.

Exclusion Criteria:

• N/A

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CASE; Patients who had an episode of diarrhoea caused by C. difficile in an hematological unit (2003-2018)	Other: No intervention; No intervention
CONTROL; Patients who have had an episode of diarrhoea not caused by C. difficile in an hematological unit (2003-2018)	Other: No intervention; No intervention
PROSPECTIVE COHORT; All patients diagnosed with an hematological/oncological disease or with any immunosuppressive condition, who have a positive detection of toxigenic Clostridium difficile in 2019.	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence	number of CDI cases/ 10,000 patient days	2006-2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of CDI	The percentage of recurrent CDI episodes with respect of the total number of CDI cases	2006-2020
Mortality attributable to CDI	Percentage of patients with CDI whose death is attributed to CDI	2006-2020

Collaborators and Investigators

• Sponsor: Hospital General Universitario Gregorio Marañon
• Investigators: Principal Investigator: Elena Reigadas, PharmD, PhD, Hospital General Universitario Gregorio Marañon

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 24, 2019
• First Posted (Actual): May 28, 2019

Study Record Updates

• Last Update Posted (Actual): July 29, 2020
• Last Update Submitted That Met QC Criteria: July 28, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: recurrence; hematologic conditions
• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Diarrhea; Clostridium Infections
• Other Study ID Numbers: MICRO.HGUGM.2017-018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No