Developing the tools to fight drug-resistant bacteria
| ISRCTN | ISRCTN12956554 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12956554 |
| Secondary identifying numbers | 965265 |
- Submission date
- 01/11/2021
- Registration date
- 11/11/2021
- Last edited
- 09/04/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Background and study aims
Antibiotic resistance is one of the foremost concerns of modern medicine. While antibiotics have saved countless lives, emerging resistant bacteria (for which many antibiotics do not work) are endangering the well-being of future generations. We need to take action to reduce the effects of these infections. The EU-funded REVERSE project will develop a framework to help prevent, manage, and limit the impact of drug-resistant bacteria. The project will use expertise from many different disciplines in a combined action plan for hospitals. This will also help to develop new strategies to fight resistant bacteria and reduce their effect on health and the European economy.
Who can participate?
Adult inpatients in intensive care, internal medicine, haematology-oncology, and surgery (including transplant units) at hospitals in four European countries with high rates of infections caused by resistant bacteria.
What does the study involve?
Three programmes will be started one after the other to try and reduce these infections. All hospitals will start the programmes but at different times. Some of the hospitals will also have additional help to make sure these programmes are put in place. Some of the data collected include hospital antibiotic use, hand sanitizer use, and hospital infection numbers. The researchers will also do a cost analysis to look at whether these programmes saved money by preventing infections. For this, some patients in the hospital will be asked questions about their quality of life after they leave the hospital.
What are the possible benefits and risks of participating?
There is no additional risk to patients beyond that of a regular hospital admission. The potential benefits to patients include reduced rates of infection with resistant bacteria.
Where is the study run from?
University of Zurich (Switzerland)
When is the study starting and how long is it expected to run for?
July 2021 to June 2026
Who is funding the study?
European Union Horizon 2020 research and innovation programme
Who is the main contact?
Ashlesha Sonpar
reverse@usz.ch
Contact information
Dr Ashlesha Sonpar
Scientific
Scientific
Klinik für Infektionskrankheiten und Spitalhygiene
UniversitätsSpital Zürich
Rämistrasse 100
Zurich
8091
Switzerland
| Phone | +41 (0)44 255 4310 |
|---|---|
| reverse@usz.ch |
Study information
| Study design | Hybrid type 2 effectiveness-implementation study; prospective multi-centre cluster-randomized stepped-wedge trial with nested cohort study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Cluster randomised trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | 40607_PIS_participants.pdf |
| Scientific title | pREVention and management tools for rEducing antibiotic Resistance in high prevalence SEttings |
| Study acronym | REVERSE |
| Study objectives | Rationale: Develop and implement cost-effective strategies and tools for the prevention and clinical management of healthcare-associated infections due to multidrug-resistant pathogens, and to reduce the burden of antimicrobial resistance in high prevalence care settings. |
| Ethics approval(s) | Approved 07/01/2022, Kantonale Ethikkommission (Stampfenbachstrasse 121, 8090 Zürich, Switzerland; +41 (0)43 259 79 70; info.kek@kek.zh.ch), ref: AO-2021-00078 |
| Health condition(s) or problem(s) studied | Antimicrobial resistance |
| Intervention | Three bundled programmes will be sequentially implemented after a minimum 6-month baseline monitoring period - microbiology and diagnostic stewardship (MDS), infection prevention and control (IPC), and antimicrobial stewardship (ABS). These interventions target the institutions and health professionals. The data will be collected throughout the baseline and intervention periods. The details of the MDS, IPC, and ABS interventions are as follows (please note: not all interventions within a programme will start immediately): MDS: 1. Guidance document on the usage of diagnostics for suspected bacterial infection 2. Audit and feedback on compliance to guidance 3. Universal screening in high-risk settings and abdominal surgery patients (intensive care, haemato-oncology, transplant units); 4. Molecular characterization of blood cultures and samples from lower respiratory tracts (HAP) to inform ABS 5. Rapid tests if molecular tests are unavailable (e.g. CARBA-5 or beta-LACTA) 6. Molecular characterization of isolated CRE from repetitive colonisation surveys to inform IPC. IPC: 1. Enhanced standard precautions (e.g., use of gloves for contacts with wounds and body fluids) and hand hygiene, with special emphasis on the use of alcohol-based hand rub (ABHR) 2. Regular point prevalence surveys to detect previously unknown multidrug-resistant organism (MDRO) carriers and identify hidden hot spots of MDRO transmission in the concerned institution in collaboration with WP2MDS 3. Reinforced basic environmental hygiene 4. Targeted MDRO screening at admission for selected high-risk populations (e.g., previously known MDRO carriers) 5. Audits and feedback on the basic IPC components in regular time intervals 6. Enhanced, universal MDRO screening at admission in ICUs and other high-risk units 7. Reinforced contact precautions for identified MDRO carriers 8. Enhanced cleaning in high-risk settings with point prevalence sampling surveys 9. Improved information transfer on MDRO's carriage status within the hospital and along the referral pathways 10. Root-cause analysis of newly detected cases to direct infection control measures 11. Setup and implementation of advanced cohorting facilities for selected highly resistant MDROs (e.g., CRE) 12. Dedicating nursing staff for patient care with highly resistant MDROs 13. Decolonization or decontamination of colonized patients or patients in high-risk units using chlorhexidine body wash 14. Molecular analysis and sequencing of isolates for outbreak investigation (please see 3.4.4 for details) 15. The organisational and pharmaceutical interventions will be started with the basic best practices bundle. ABS: 1. Establishment of a multidisciplinary stewardship committee 2. Guidance document on syndrome-specific treatment pathways 3. Dedicated recommendations for new drugs 4. Training on judicious antibiotic prescription 5. Audit and feedback on compliance to guidance on antibiotic use 6. Stewardship rounds two times a week in high-risk settings (intensive care, haematology-oncology, transplant units) 7. Pathways for integration of antibiotic consumption reporting to the stewardship policies 8. Weekly stewardship rounds in wards other than high-risk, but with a high prevalence of AMR 9. Integration of screening results in the decision-making process for empiric therapy for severe bacterial infections in immunocompromised patients 10. Integration of screening results before abdominal surgery for personalised prophylaxis 11. Integration of molecular characterization of cultures to drive targeted therapy of bloodstream infections and hospital-acquired pneumonia All centres will have a point prevalence survey for CRE colonization at three predefined time points. Positive swabs may be sequenced to assess for clonality and to establish transmission links. At two timepoints in the study, an audit will be done to assess microbiology capabilities. In addition, before the IPC module, hospitals will be randomised to either basic implementation support (12 BASIC study sites) or enhanced implementation support (12 ENHANCE study sites) as part of the hybrid approach. This randomisation applies only to the implementation part of this study. The hospitals will be stratified by country and cluster-randomized in a stepped wedge design. A cost-effectiveness analysis will be done at the end to assess the feasibility of expanding such an initiative. Part of this cost-effectiveness analysis includes a cohort study comparing the quality of life post-discharge of patients with hospital-acquired multi-drug resistant infections to patients without such infections. The cohort study will use validated questionnaires at baseline, 1, 3, 6, and 12 months post-discharge. There will be detailed costing data obtained from the hospitals to accurately estimate the investment required to sustain these initiatives. |
| Intervention type | Other |
| Primary outcome measure | Incidence density (N/1000 patient-days) of healthcare-acquired infections due to carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant enterobacteriales (CRE), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), measured by prospective surveillance using laboratory and chart information every 3 months starting at baseline and continuing until the end of the study |
| Secondary outcome measures | 1. Quarterly proportions of HAI due to CRE, CRPA, and CRAB measured by prospective surveillance using laboratory and chart information every 3 months starting at baseline and continuing until the end of the study 2. Incidence density (N/1000 patient-days) of healthcare-associated bloodstream infection of any type measured using existing surveillance in hospitals every 3 months starting at baseline and continuing until the end of the study 3. Incidence density (N/1000 patient-days) and quarterly proportions of HAI due to other clinically important multidrug-resistant organisms (such as ESBL-producing Klebsiella pneumonia, methicillin-resistant Stapyhlococcus aureus, and vancomycin-resistant enterococci) measured using existing surveillance in hospitals every 3 months starting at baseline and continuing until the end of the study 4. Incidence density (N/10,000 patient-days) of Clostridium difficile infection (as a proxy for the consumption of broad-spectrum antibiotics) measured using existing surveillance in hospitals every 3 months starting at baseline and continuing until the end of the study 5. Performed blood culture sets per 1000 patient-days measured using laboratory data every 3 months starting at baseline and continuing until the end of the study 6. Performed stool tests for Clostridioides difficile per 1000 patient-days measured using laboratory data every 3 months starting at baseline and continuing until the end of the study 7. Consumption of alcohol-based handrub solution per 1000 patient-days measured using administrative data every 3 months starting at baseline and continuing until the end of the study 8. Antimicrobial consumption in daily-defined doses over the last 3 months measured using administrative data every 3 months starting at baseline and continuing until the end of the study 9. Prevalence of CRE colonisation measured via rectal swabs at the beginning of the infection prevention and control programme (IPC), at the end of the IPC programme, and at the end and at the end of the antibiotic stewardship programme 10. Resistance mechanisms of the isolated CRE in the three prevalence surveys, assessed using molecular techniques at the beginning of the infection prevention and control programme (IPC), at the end of the IPC programme, and at the end and at the end of the antibiotic stewardship programme 11. Clonality of the isolated CRE in the three prevalence surveys assessed using whole-genome sequencing at the beginning of the infection prevention and control programme (IPC), at the end of the IPC programme, and at the end and at the end of the antibiotic stewardship programme 12. In-hospital all-cause mortality over the last 3 months measured using administrative data every 3 months starting at baseline and continuing until the end of the study 13. Re-admissions density (N / month) of any type measured using administrative data every 3 months starting at baseline and continuing until the end of the study 14. Length of hospital stay for admissions of any type, reported as the average length of stay over the last 3 months, measured using administrative data every 3 months starting at baseline and continuing to the end of the study 15. Intervention (MDS, IPC and ABS) fidelity, acceptability, feasibility, and sustainability measured through surveys of healthcare personnel after workshops or at the end of the intervention period |
| Overall study start date | 01/07/2021 |
| Completion date | 30/06/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 24 centres |
| Key inclusion criteria | All adult inpatients in participating centers in intensive care, internal medicine, haematology-oncology, and surgery (including transplant units) |
| Key exclusion criteria | 1. Patients in settings other than mentioned above 2. Children, infants, or neonates |
| Date of first enrolment | 01/03/2022 |
| Date of final enrolment | 30/09/2022 |
Locations
Countries of recruitment
- Greece
- Italy
- Romania
- Spain
Study participating centres
Azienda Ospedaliera Universitaria Integrata Verona
Piazzale L.A. Scuro, 10
Verona
37134
Italy
Verona
37134
Italy
Policlinico Universitario A. Gemelli Rome
Via della Pineta Sacchetti 217
Rome
00168
Italy
Rome
00168
Italy
Policlinico S.Orsola Bologna
Via Giuseppe Massarenti 9
Bologna
40138
Italy
Bologna
40138
Italy
ASST Santi Paolo e Carlo Milano
Via Antonio di Rudinì 8
Milan
20142
Italy
Milan
20142
Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano
Ospedale Maggiore Policlinico Milano
Via Francesco Sforza 35
Milan
20122
Italy
Via Francesco Sforza 35
Milan
20122
Italy
IRCCS Ospedale Sacro Cuore Don Calabria
Don A. Sempreboni, 5
Negrar di Valpolicella
37024
Italy
Negrar di Valpolicella
37024
Italy
Hospital Universitario Jerez de la Frontera
Ctra. Trebujena, s/n
Jerez de la Frontera
11407
Spain
Jerez de la Frontera
11407
Spain
Hospital Universitario Reina Sofía
Av. Menendez Pidal, s/n
Cordoba
14004
Spain
Cordoba
14004
Spain
Hospital Universitario Son Espases
Carretera de Valldemossa 79
Palma
07120
Spain
Palma
07120
Spain
Hospital del Mar
Passeig Marítim de la Barceloneta 25, 29
Barcelona
08003
Spain
Barcelona
08003
Spain
Hospital General Universitario de Alicante
Pintor Baeza 11
Alicante
03010
Spain
Alicante
03010
Spain
Hospital Álvaro Cunquiero
Estrada de Clara Campoamor 341
Vigo
36213
Spain
Vigo
36213
Spain
Laiko General Hospital
Agiou Thoma 17
Athens
115 27
Greece
Athens
115 27
Greece
Ippokrateio General Hospital
Vasilissis Sofias 114
Athens
11527
Greece
Athens
11527
Greece
AHEPA University Hospital of Thessaloniki
Kiriakidi 1
Thessaloniki
546 21
Greece
Thessaloniki
546 21
Greece
University Hospital of Ioannina
Niarxou Avenue
Ioannina
45500
Greece
Ioannina
45500
Greece
Attikon General Hospital
Rimini 1
Chaidari
124 62
Greece
Chaidari
124 62
Greece
Military Hospital Bucharest
Calea Plevnei Nr. 134
Bucharest
010825
Romania
Bucharest
010825
Romania
University Emergency Hospital Bucharest
Splaiul Independenței 169
Bucharest
050098
Romania
Bucharest
050098
Romania
Timisoara Municipal Clinical Emergency Hospital
Strada Daliei Nr. 17
Timisoara
300254
Romania
Timisoara
300254
Romania
Targu Mures County Hospital
Str. Gh. Marinescu Nr. 1
Targu Mures
540103
Romania
Targu Mures
540103
Romania
Sibiu County Emergency Hospital
Bulevardul Corneliu Coposu 2-4
Sibiu
550245
Romania
Sibiu
550245
Romania
Fundeni Hospital
Sos Fundeni Nr. 258, Sector 2
Bucharest
022328
Romania
Bucharest
022328
Romania
Sismanoglio General Hospital
Sismanogliou 37
Marousi
151 26
Greece
Marousi
151 26
Greece
Sponsor information
University Hospital of Zurich
Hospital/treatment centre
Hospital/treatment centre
Clinic for Infectious Diseases and Hospital Hygiene
Rämistrasse 100
Zurich
8091
Switzerland
| Phone | +41 (0)43 253 03 52 |
|---|---|
| walter.zingg@uzh.ch | |
| Website | http://www.uzh.ch/index_en.html |
"ROR" |
https://ror.org/01462r250 |
Funders
Funder type
Government
Horizon 2020
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- EU Framework Programme for Research and Innovation, Horizon 2020 - Research and Innovation Framework Programme, European Union Framework Programme for Research and Innovation
Results and Publications
| Intention to publish date | 30/01/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 1. Results will be published in peer-reviewed journals with open access policies where possible. 2. Periodic reports will be distributed to stakeholders and the funding agency 3. Participant level data is only collected for the quality of life study (observational). Only hospital-level data or surveys are utilized for the rest of the study. Aggregate data will be available upon request |
| IPD sharing plan | The following applies to persons outside of the REVERSE consortium. The data will be available after publication. The project email can be used to contact the coordinating team regarding data requests (reverse@usz.ch). Data will be made available where possible to support further research under FAIR principles, except for data that are confidential or cannot be shared under the GDPR regulations. De-identified hospital-level data (e.g.: data on hospital-acquired infection rates, antimicrobial use, ABHR use, or cost data) needed to verify the results will be available for approximately 5 years after the project ends. De-identified and aggregate data from the cohort study needed to verify results will also be available for approximately 5 years after the project ends. Please note, participant-level data from the cohort study will not be available due to patient-level confidential information. The researchers will share data electronically with other research groups conducting meta-analyses or reviews on IPC, ABS, or MDS interventions. This adheres to the data-sharing rules outlined in the Grant Agreement with the European Commission. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participants | 10/11/2021 | No | Yes | |
| Participant information sheet | Representatives | 10/11/2021 | No | Yes | |
| Protocol file | version 1.1 | 10/01/2022 | 16/02/2022 | No | No |
| Participant information sheet | Brochure for participants version 2 |
06/12/2022 | 05/02/2024 | No | Yes |
| Protocol file | version 1.4 | 15/06/2023 | 05/02/2024 | No | No |
| Statistical Analysis Plan | 09/04/2024 | No | No |
Additional files
- 40607_PIS_participants.pdf
- Participants
- 40607_PIS_representatives.pdf
- Representatives
- ISRCTN12956554_Protocol_v1.1_10Jan2022.pdf
- ISRCTN12956554_Protocol_v1.4_15June2023.pdf
- ISRCTN12956554_Brochure_v2_06Dec2022.pdf
- Brochure for participants
- ISRCTN12956554 SAP.pdf
Editorial Notes
09/04/2024: The statistical analysis plan was uploaded as an additional file.
05/02/2024: The following changes were made:
1. A protocol file has been uploaded.
2. A brochure for participants was uploaded.
29/03/2022: The following changes were made to the trial record:
1. The trial participating centre Genimatas Hospital was removed.
2. The trial participating centre Sismanoglio General Hospital was added.
16/02/2022: The following changes have been made:
1. A protocol file has been uploaded.
2 The ethics approval information has been updated.
10/01/2022: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/01/2022 to 01/03/2022.
2. Some of the trial participating centre addresses were corrected.
09/11/2021: Trial's existence confirmed by the European Commission.
