Burden of Antibiotic Resistance in Gram-Negative Infections in Dutch Hospitals (GRAND-ABC)
|ClinicalTrials.gov Identifier: NCT02007343|
Recruitment Status : Active, not recruiting
First Posted : December 10, 2013
Last Update Posted : October 31, 2016
|Condition or disease|
|Infection Resistant to Drugs Gram-Negative Bacterial Infection|
This study addresses the following three aims:
- To provide a more accurate estimate than currently available of the incremental disease burden and attributable costs of antibiotic-resistant as compared to antibiotic-sensitive gram-negative bacteria (i.e. Enterobacteriaceae and non-fermenters). This analysis is focused on gram-negative infections for which patients are hospitalized. In a less detailed manner, the same analysis of disease burden and costs can be performed for acquiring a gram-negative infection during hospitalization.
- To identify determinants associated with resistance in gram-negative infections, to the extent that they are confounders of the relation between resistance and outcome.
- To adapt and optimize existing methodology to measure the burden of resistance, among others by calculating disability-adjusted life years (DALYs) which incorporate not merely mortality, but also morbidity.
GRAND-ABC is designed as a prospective parallel matched cohort, which will run for a year in each of the eight participating hospitals. The primary cohort is a random sample of all Gram-negative infections occurring in a participating hospital during the study period. This cohort can be divided on the basis of the primary determinant status (whether the Gram-negative pathogen is resistant or not based on Dutch guideline for multi-drug resistant organisms; Werkgroep Infectiepreventie (WIP). Bijzonder resistente micro-organismen (BRMO). December 2012. http://www.wip.nl/free_content/Richtlijnen/130424_BRMO.pdf) into two parallel subcohorts. Each patient in each of the subcohorts will be matched to one patient without a gram-negative infection. Together these will form the secondary cohort of non-infected patients: patients admitted to the hospital during the study period who are within the same risk set as the infected patients.
For all patients data collection will be performed by review of medical files, which will cover the entire admission during which they were included in the study, and all cause 30 day mortality. Data collection for the hospital stay covers confounders and effect modifiers of the associations studied, and feeds into the outcomes costs, DALYs and length of stay. For the cohort with gram-negative infections, data on infection parameters and antibiotic treatment parameters are also collected.
In addition, the subcohort with infections by multi-drug resistant organisms and a random 20% of the subcohort with infections by sensitive organisms will be selected for follow-up, consisting of sending questionnaires and renewed medical file review 30 days after the index culture date. In the case of ongoing sequelae of the gram-negative infection, this procedure is repeated 90 days after the index culture date. These questionnaires will feed into the outcomes costs, DALYs and quality-adjusted life years (QALYs).
|Study Type :||Observational|
|Estimated Enrollment :||4050 participants|
|Official Title:||The Attributable Burden and Costs of Infections Caused by Antibiotic-Resistant Gram-Negative Bacteria in Dutch Hospitals|
|Study Start Date :||June 2013|
|Actual Primary Completion Date :||May 2016|
|Estimated Study Completion Date :||December 2016|
Patients with gram-negative infections
Sample (5/week/hospital) of all patients in a hospital that meet all of the following:
Date of entry into cohort: date of index culture of infection episode
Matched sample of all patients that (1) were admitted to the hospital and (2) did not have a gram-negative infection according to the 4 criteria set out in the other group on the date used for matching. Selected by matching 1:1 to patients with gram-negative infections on (1) hospital, (2) length of hospital stay on the date the index culture for the infected patient was obtained, and (3) age.
Date of cohort entry: date of index culture of matched infected patient
- All cause mortality [ Time Frame: Up to 30 days ]Death (whether in-hospital or after discharge) from any cause, as apparent from medical record or municipal registry.
- Costs [ Time Frame: Hospital stay (all patients; expected average 1 week) and up to 90 days (follow-up patients) ]
Costs generated from societal perspective, including:
- Direct costs within healthcare sector, based on relating standard Dutch reference prices to (1) restricted chart review for all patients, (2) extensive collection of cost data in two of eight participating hospitals, (3) health care use after discharge, as recorded from medical files and reported by patients in questionnaires
- Other direct costs (own out-of-pocket expenses and time invested by caregivers), as reported by patients in questionnaires
- Indirect productivity losses, as reported by patients in questionnaires
- (possibly) Decision-analytic modelling of costs generated by sequelae not within 90 days of index culture date
Questionnaires are not available for the non-infected cohort, and therefore the costs for acquiring gram-negative infections can only be calculated from the hospital perspective.
- DALYs [ Time Frame: Up to 90 days ]
Years of Life Lost (YLL) and Years Lived with Disability (YLD) attributable to infection as apparent from an outcome tree of health outcomes related to gram-negative infections. This tree is preconceived, but modifiable according to observed sequelae in the study. A mathematical model for this outcome will be constructed that incorporates, apart from the observed sequelae in the study, factors such as (1) preexisting decreased life expectancy and quality of life due to comorbidity, (2) known transition parameters between health outcomes from literature, (3) confounding effects of comorbidity on transition parameters, (4) sequelae not observed within the time frame of data collection for the study, (5) 'baseline' change in health outcomes during hospitalization as apparent from the non-infected cohort, and (6) occupancy of several health outcome simultaneously.
This outcome will not be calculated for the non-infected cohort.
- Length of stay [ Time Frame: Hospital stay (expected average 1 week) ]Number of days until hospital discharge.
- QALYs [ Time Frame: Up to 90 days ]
Measured by EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) in questionnaires, as a confirmation of the DALY model results.
This outcome will not be calculated for the non-infected cohort.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02007343
|Meander Medisch Centrum|
|St. Antonius Ziekenhuis|
|St. Elisabeth Ziekenhuis|
|Principal Investigator:||Marc JM Bonten, MD PhD||UMC Utrecht, Utrecht, the Netherlands|
|Study Chair:||Heidi SM Ammerlaan, MD PhD||Catharina Hospital, Eindhoven, the Netherlands|