Ecological Effects of Decolonisation Strategies in Intensive Care

NCT02208154 | Completed Phase 3 DMC

• 1 other identifier: EudraCT 2012-002604-41
• Study Type: interventional
• Target: 8,665
• Locations: 6 countries
• Sites: 13

Brief Summary

Previous research has shown that applying certain treatments can reduce both the number of infections and the presence of resistant bacteria in the intensive care (ICU) and its patients. These treatments have been used as standard care throughout the world for many years, but they have not been compared to each other yet. The investigators aim to evaluate the effect of 3 different treatments on the occurrence of resistant bacteria and bacterial infections in the ICU and to establish which treatment is the best. All adult patients undergoing mechanical ventilation are eligible for this study and will receive treatment according to the study scheme. Twice weekly, sputum and rectal samples will be obtained to measure the effects. All ICU-patients will receive standard treatment, consisting of daily body washing with an antiseptic (chlorhexidine 2%), oral care and a hand-hygiene program for health care workers as endorsed by the WHO. According to 4 different study periods, each participant will receive one of the following extra treatments depending on his or her admission date:

• Standard treatment only (this is the control group)
• Chlorhexidine 1% oral gel, this is an antiseptic.
• Antibiotic mouth paste containing 3 different antibiotics (selective oropharyngeal decontamination, SOD).
• Antibiotic mouth paste and suspension for the stomach and intestines containing 3 different antibiotics (selective digestive decontamination, SDD). All treatments will be given 4 times daily with the purpose of killing harmful bacteria in the mouth (CHX, SOD,SDD) and digestive tract (SDD). During the study the investigators will examine the effect of these treatments on:
• the occurrence of blood stream infections with certain bacteria
• cross-transmission of certain bacteria between patients
• presence of these bacteria in the respiratory tract of the patients
• patient survival Benefits: Previous research has shown that these interventions can reduce infections in intensive care patients. Risks: The interventions performed (both cultures and treatment) are considered safe and are already given as standard care in many ICUs throughout the world. There is a slight risk that bacteria become resistant to antibiotics: this will be monitored closely during the trial.

Conditions

ICU-ecology (Multidrug Resistant Bacteria); ICU-acquired Bacteraemia

Keywords

ICU acquired bacteraemia; colonization; decolonization; selective decontamination; multidrug resistant bacteria

Outcome Measures

Primary Outcomes (1)

• ICU-Ecology

  To determine the ecological effects of decolonisation regimens (SDD, SOD and CHX-Oro) in reducing (MDR-GNB) ICU-acquired bacteraemia when compared to standard care.

  27 months

Secondary Outcomes (7)

• Cross-transmission rates

  27 months

• Respiratory tract colonization

  27 months

• ward-level systemic antibiotic use

  27 months

• colonization in relation to bacteraemia

  27 months

• transmission capacities of different bacteria

  27 months

Study Arms (4)

Standard care

ACTIVE COMPARATOR

Standard infection prevention measurements will be implemented before the baseline period and carried out throughout the entire trial. They consist of: * Chlorhexidine 2% body washings (CHX-BW) for all ICU patients. The face and neck of the patient will not be cleansed with Chlorhexidine to prevent irritation of the eyes and face. * A hand hygiene improvement program (HHIP) based on the program designed by the World Health organisation (WHO). * Standard oropharyngeal care consists of oral washing with sterile water (3-4 times daily) and tooth brush twice daily.

Drug: Chlorhexidine oral care (CHX-Oro); Drug: Selective oropharyngeal decontamination (SOD); Drug: Selective Digestive Decontamination (SDD)

Chlorhexidine oral care (CHX-Oro)

EXPERIMENTAL

Chlorhexidine digluconate oromucosal gel 1%, 2cm, to be administered 4 times daily, during invasive mechanical ventilation.

Drug: Chlorhexidine oral care (CHX-Oro)

Selective oropharyngeal decontamination

EXPERIMENTAL

Selective oropharyngeal decontamination (SOD) mouth paste containing colistin and tobramycin in a 2% concentration and nystatin 1 x 10\^5 units, dosage 0.5g , to be administered 4 times daily during the entire period of invasive mechanical ventilation.

Drug: Selective oropharyngeal decontamination (SOD)

Selective digestive decontamination

EXPERIMENTAL

Selective digestive decontamination (SDD), suspension via the nasogastric tube containing 100 mg colistin, 80 mg tobramycin and nystatin 2 x 10\^6 i.u., dosage 10ml, to be administered together with SOD (see above) 4 times daily during entire period of mechanical ventilation.

Drug: Selective Digestive Decontamination (SDD)

Interventions

Chlorhexidine oral care (CHX-Oro) DRUG

Oromucosal gel consisting of chlorhexidine 1%, administered 4 times daily.

Also known as: Chlorhexidine digluconate, CHX-Oro, Chlorhexidine 1% oromucosal gel, Corsodyl dental gel

Chlorhexidine oral care (CHX-Oro); Standard care

Selective oropharyngeal decontamination (SOD) DRUG

SOD consists of application of a paste containing colistin, tobramycin in a 2% concentration and nystatin 1 x 10\^5 units. SOD will be applied to the mouth 4 times daily until extubation.

Also known as: SOD

Selective oropharyngeal decontamination; Standard care

Selective Digestive Decontamination (SDD) DRUG

SDD consists of both: * SOD (described elsewhere) * AND 10 ml of an enteric suspension containing 100 mg colistin, 80 mg tobramycin and nystatin 2 x 10\^6 i.u, to be administered via the nasogastric tube. The combination is administered 4 times daily (Unlike in previous studies, systemic antibiotics are not a part of SDD)

Also known as: SDD

Selective digestive decontamination; Standard care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• mechanical ventilation (only invasive ventilation: i.e. intubated patients or patients with tracheostomal ventilation)
• no planned extubation within 24 hours When mechanical ventilation is not started directly after admission but later in the course of their ICU stay, patients are still eligible to participate.

You may not qualify if:

• patients under the age of 18
• patients with known allergy to any of the medications or agents used (i.e. colistin, tobramycin, nystatin or chlorhexidine )
• pregnancy
• Participation ends as soon as the patient is extubated or after tracheostomal ventilation has stopped (weaning completed).

Sponsors & Collaborators

• MJM Bonten: lead
• Paris 12 Val de Marne University: collaborator

Study Sites (13)

Universitair Ziekenhuis Antwerpen

Edegem, B-2650, Belgium

Location

Algemeen Ziekenhuis Sint Lucas

Ghent, 9000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

CHU Liege

Liège, 4000, Belgium

Location

Clinique Saint-Pierre Ottignies

Ottignies, 340, Belgium

Location

Ospedale San Camillo

Rome, 00152, Italy

Location

Hospital Geral de Santo António (Centro Hospitalar do Porto, EPE)

Porto, 4099-001, Portugal

Location

Centro Hospitalar de Trás-os-Montes e Alto Douro, EPE

Vila Real, 5000 - 508, Portugal

Location

University clinic of respiratory and allergic diseases

Golnik, 4204, Slovenia

Location

Hospital Clinic of Barcelona

Barcelona, 08036, Spain

Location

l'Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario y Politécnico La Fé de Valencia

Valencia, 46026, Spain

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Related Publications (6)

• de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Bogaers-Hofman D, van der Meer NJ, Bernards AT, Kuijper EJ, Joore JC, Leverstein-van Hall MA, Bindels AJ, Jansz AR, Wesselink RM, de Jongh BM, Dennesen PJ, van Asselt GJ, te Velde LF, Frenay IH, Kaasjager K, Bosch FH, van Iterson M, Thijsen SF, Kluge GH, Pauw W, de Vries JW, Kaan JA, Arends JP, Aarts LP, Sturm PD, Harinck HI, Voss A, Uijtendaal EV, Blok HE, Thieme Groen ES, Pouw ME, Kalkman CJ, Bonten MJ. Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med. 2009 Jan 1;360(1):20-31. doi: 10.1056/NEJMoa0800394.

  PMID: 19118302 BACKGROUND

• Edwards SJ, Braunholtz DA, Lilford RJ, Stevens AJ. Ethical issues in the design and conduct of cluster randomised controlled trials. BMJ. 1999 May 22;318(7195):1407-9. doi: 10.1136/bmj.318.7195.1407. No abstract available.

  PMID: 10334756 BACKGROUND

• Funk MJ, Westreich D, Wiesen C, Sturmer T, Brookhart MA, Davidian M. Doubly robust estimation of causal effects. Am J Epidemiol. 2011 Apr 1;173(7):761-7. doi: 10.1093/aje/kwq439. Epub 2011 Mar 8.

  PMID: 21385832 BACKGROUND

• McCaffrey DF, Griffin BA, Almirall D, Slaughter ME, Ramchand R, Burgette LF. A tutorial on propensity score estimation for multiple treatments using generalized boosted models. Stat Med. 2013 Aug 30;32(19):3388-414. doi: 10.1002/sim.5753. Epub 2013 Mar 18.

  PMID: 23508673 BACKGROUND

• Rajakani SG, Xavier BB, Nguyen NM, Lin Q, Braspenning A, Plantinga NL, Wittekamp BHJ, Zarkotou O, Van Houdt R, Glupczynski Y, Pournaras S, Bonten MJM, Malhotra-Kumar S. Characterization of genome-wide transpositions induced by colistin exposure in multi-drug-resistant Klebsiella pneumoniae. Antimicrob Agents Chemother. 2025 Jul 2;69(7):e0157424. doi: 10.1128/aac.01574-24. Epub 2025 May 19.

  PMID: 40387400 DERIVED

• Wittekamp BH, Plantinga NL, Cooper BS, Lopez-Contreras J, Coll P, Mancebo J, Wise MP, Morgan MPG, Depuydt P, Boelens J, Dugernier T, Verbelen V, Jorens PG, Verbrugghe W, Malhotra-Kumar S, Damas P, Meex C, Leleu K, van den Abeele AM, Gomes Pimenta de Matos AF, Fernandez Mendez S, Vergara Gomez A, Tomic V, Sifrer F, Villarreal Tello E, Ruiz Ramos J, Aragao I, Santos C, Sperning RHM, Coppadoro P, Nardi G, Brun-Buisson C, Bonten MJM. Decontamination Strategies and Bloodstream Infections With Antibiotic-Resistant Microorganisms in Ventilated Patients: A Randomized Clinical Trial. JAMA. 2018 Nov 27;320(20):2087-2098. doi: 10.1001/jama.2018.13765.

  PMID: 30347072 DERIVED

Related Links

• Website of Consortium R-GNOSIS

MeSH Terms

Interventions

chlorhexidine gluconate; Chlorhexidine

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Marc JM Bonten, Prof.

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

• Christian Brun-Buisson, Prof.

  UPEC Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Molecular Epidemiology of Infectious Diseases

Model Details: This study is a cluster-randomized multicenter study with crossover of interventions within study centers. The first study period is always the baseline period. After six months, the first intervention period (order is determined by randomization) is implemented, followed by the second and third intervention. The intervention periods are separated by a wash out period of one month.

Study Record Dates

• First Submitted: July 22, 2014
• First Posted: August 4, 2014
• Study Start: December 1, 2013
• Primary Completion: October 27, 2017
• Study Completion: October 27, 2017
• Last Updated: November 1, 2017

Record last verified: 2017-10

Locations

BE (5); ES (3); SL (1); GB (1); IT (1); PT (2)