Infection Resistant to DrugsGRAND-ABCNCT02007343
Burden of Antibiotic Resistance in Gram-Negative Infections in Dutch Hospitals
An observational study of Infection Resistant to Drugs and Gram-Negative Bacterial Infection, run by UMC Utrecht at 8 sites in Netherlands.
Trial summary
This study aims to assess how large an additional disease burden and what extra costs are generated by antibiotic resistance in patients suffering from infections caused by gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa, in hospitals in the Netherlands. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infection Resistant to Drugs, Gram-Negative Bacterial Infection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 3,895 participants
- Where
- 8 sitesNetherlands
- Study dates
- Jun 2013to May 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients admitted to hospitals
Who may be able to join
- Please refer to descriptions of two cohorts
Who cannot join
- Patients on children's wards
- Patients admitted to wards for long-term care or psychiatric wards, that were not subsequently admitted to acute care wards as a consequence of the infection
- Patients admitted to wards that are excluded for logistic reasons such as the non-availability of electronic patient files, that were not subsequently admitted to included acute care wards as a consequence of the infection
- Patients that have been included in the cohort of infected patients during the same hospitalization or within the past 30 (if not eligible for follow-up) or 90 (if eligible for follow-up) days
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Netherlands8 sites
Meander Medisch Centrum
Amersfoort
Amphia Ziekenhuis
Breda
Catharina Ziekenhuis
Eindhoven
Tergooi
Hilversum
St. Antonius Ziekenhuis
Nieuwegein
St. Elisabeth Ziekenhuis
Tilburg
Diakonessenhuis
Utrecht
UMC Utrecht
Utrecht
About this study
Official title: The Attributable Burden and Costs of Infections Caused by Antibiotic-Resistant Gram-Negative Bacteria in Dutch Hospitals
This study aims to assess how large an additional disease burden and what extra costs are generated by antibiotic resistance in patients suffering from infections caused by gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa, in hospitals in the Netherlands.
Read the detailed description
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).
- Keywords
- Enterobacteriaceae, Pseudomonas, Acinetobacter, Stenotrophomonas, Mortality, Morbidity, Cost of Illness, Causality, Multicenter Study, Cohort Studies, Case-Control Studies, Prospective Studies, Follow-up Studies
- Medical subject headings
- Gram-Negative Bacterial Infections, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with gram-negative infections | Sample (5/week/hospital) of all patients in a hospital that meet all of the following: * meeting the criteria of at least one infection entity based on (modified) definitions of the Center for Disease Control and Infection Prevention (CDC; Am J Infect Control 2008;36:309-32) (restricted to infections that have septic potential); * a culture with a gram-negative isolate (Enterobacteriaceae / Pseudomonas aeruginosa / Acinetobacter spp. / Stenotrophomonas maltophilia) with minimal inhibitory concentration (MIC) results from an automated system available that can be used to identify such an infection entity according to these criteria; * receipt of antibiotics (oral, intravenous or intramuscular) for this infection, the choice of which is determined by the culture with the gram-negative (i.e. this isolate is seen as the causative pathogen); * were admitted to the hospital during (part of) the infection episode. Date of entry into cohort: date of index culture of infection episode | |
| Non-infected patients | 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
All cause mortality
Death (whether in-hospital or after discharge) from any cause, as apparent from medical record or municipal registry.
Measured: Up to 30 days
Secondary outcomes (3)
Costs
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.
Measured: Hospital stay (all patients; expected average 1 week) and up to 90 days (follow-up patients)
DALYs
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.
Measured: Up to 90 days
Length of stay
Number of days until hospital discharge.
Measured: Hospital stay (expected average 1 week)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2013 (estimated)
- Study startJun 2013
- Primary completionMar 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infection Resistant to DrugsStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 3,895 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, MJM Bonten, UMC Utrecht
- Investigators
- Marc JM Bonten, MD PhD, Principal investigator, UMC Utrecht, Utrecht, the NetherlandsHeidi SM Ammerlaan, MD PhD, Study chair, Catharina Hospital, Eindhoven, the Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02007343
- Sponsor's protocol ID
- GRAND-ABC
- Other IDs
- 205200007
- Acronym
- GRAND-ABC
- Status last verified
- Nov 2019
- First submitted
- 30 Oct 2013
- Last updated
- 8 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Attributable Burden and Costs of Infections Caused by Antibiotic-Resistant Gram-Negative Bacteria in Dutch Hospitals
- ClinicalTrials.gov ID
- NCT02007343
- Acronym / sponsor ID
- GRAND-ABC / GRAND-ABC
- Keywords
- Enterobacteriaceae, Pseudomonas, Acinetobacter, Stenotrophomonas, Mortality, Morbidity, Cost of Illness, Causality
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 3,895 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- Jun 2013 (actual)
- Primary completion
- Mar 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 10 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to assess how large an additional disease burden and what extra costs are generated by antibiotic resistance in patients suffering from infections caused by gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa, in hospitals in the Netherlands.
Detailed description
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 design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with gram-negative infections | – | –Sample (5/week/hospital) of all patients in a hospital that meet all of the following: * meeting the criteria of at least one infection entity based on (modified) definitions of the Center for Disease Control and Infection Prevention (CDC; Am J Infect Control 2008;36:309-32) (restricted to infections that have septic potential); * a culture with a gram-negative isolate (Enterobacteriaceae / Pseudomonas aeruginosa / Acinetobacter spp. / Stenotrophomonas maltophilia) with minimal inhibitory concentration (MIC) results from an automated system available that can be used to identify such an infection entity according to these criteria; * receipt of antibiotics (oral, intravenous or intramuscular) for this infection, the choice of which is determined by the culture with the gram-negative (i.e. this isolate is seen as the causative pathogen); * were admitted to the hospital during (part of) the infection episode. Date of entry into cohort: date of index culture of infection episode |
| Non-infected patients | – | –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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients admitted to hospitals
Key inclusion criteria (1 listed)
- Please refer to descriptions of two cohorts
Key exclusion criteria (4 listed)
- Patients on children's wards
- Patients admitted to wards for long-term care or psychiatric wards, that were not subsequently admitted to acute care wards as a consequence of the infection
- Patients admitted to wards that are excluded for logistic reasons such as the non-availability of electronic patient files, that were not subsequently admitted to included acute care wards as a consequence of the infection
- Patients that have been included in the cohort of infected patients during the same hospitalization or within the past 30 (if not eligible for follow-up) or 90 (if eligible for follow-up) days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
3 secondary outcomes
Costs
Time frame: Hospital stay (all patients; expected average 1 week) and up to 90 days (follow-up patients)
DALYs
Time frame: Up to 90 days
Length of stay
Time frame: Hospital stay (expected average 1 week)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc JM Bonten, MD PhD principal investigator
UMC Utrecht, Utrecht, the Netherlands
Heidi SM Ammerlaan, MD PhD study chair
Catharina Hospital, Eindhoven, the Netherlands
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infection Resistant to Drugs and Gram-Negative Bacterial Infection, run by UMC Utrecht at 8 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All cause mortality (time frame: Up to 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2019.