Simplified Selective Digestive Tract Decontamination for the Prevention of Intensive Care Unit Acquired Infections

NCT ID: NCT01798537

Last Updated: 2013-02-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

2400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-30

Study Completion Date

2015-07-31

Brief Summary

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A simplified graded gut decontamination protocol combined with rigorous bi-weekly screening and appropriate bacterial prophylaxis, will lead to a 25% reduction in the acquisition of blood stream infections and to a 25% reduction in lower airway colonization with multi drug resistant organisms. There will be no concomitant rise in gram-positive or fungal infection or a surgency of new resistance patterns.

Detailed Description

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Simplified Selective Digestive Tract Decontamination for the prevention of ICU infections in a setting of high-level antibiotic resistance

Scientific Background:

Aerobic gram-negative bacilli (AGNB), Gram-positive bacteria and fungi are responsible for hospital acquired infections. This problem is especially typical in intensive care units (ICUs) due to the complexity of disease and wide use of invasive procedures. The common use of empiric wide-range antibiotic therapy had lead to the development significant resistance of these pathogens and this group of bacteria was defined as Multi-Drug Resistant Organisms (MDRO). Among these bacteria the most important and virulent are: Carbapenem Resistant Enterobacteriaceae (CRE), Extended Spectrum Beta Lactamases (ESBL), Methicillin Resistant Staphylococcus Aureus (MRSA), Vancomycin Resistant Enterococci (VRE) as well as Fluconazol resistant Candida.

The main reservoir of these organisms is the intestinal tract, which raises the possibility that their primary eradication may lead to control of the MDRO epidemic.

Selective Digestive tract Decontamination (SDD) has been studied extensively over the last 10-15 years and there is a body of evidence that shows that this method can reduce acquired infections, bacterial drug resistance and mortality in various ICU settings. It should be pointed out however that many of these studies were performed in units with a low prevalence of infection from MDROs and that they were never performed in units were CREs are endemic. According to the described protocols, SDD was performed as a combination of an a oral antibiotic paste - Selective Oropharyngeal Decontamination (SOD) together with enteral medication given through a gastric feeding tube, as well as a few days of prophylactic intra-venous treatment with an early generation cephalosporin.

This treatment method did not become a standard of care - mostly due to the concern that new resistance will develop to the prescribed enteral antibiotics, or that there will be a rise in the prevalence of other enteral infections as VRE, Clostridium difficile or MRSA acquired infections. Despite evidence that during the SDD treatment period there was actually a reduction of drug resistance, the Center for Disease Control and prevention (CDC) and the protocols of the surviving sepsis campaign do not recommend SDD as a means of coping with the MDRO epidemic. In published SDD protocols there was a use of wide-spectrum antibiotics that covered the range of gram-positive, gram-negative bacteria and fungi, without correlation to the results of primary screening in these patients. Even though this approach did not lead to a rise in bacterial resistance, it raised enough anxiety and resistance within the caregivers to prevent its penetration to daily use. The endemic spread of CRE infection at Rambam Medical Center has lead us to focus on these pathogens in our SDD program, while performing rigorous bi-weekly screening for all bacteria. We gave enteral antibiotic treatment (Neomycin + Polymixin E) targeting AGNB, and only if the primary screening found MRSA or Fungi, did we prescribe enteral preventive treatment against them (Vancomycin or Nystatin). Therefore, a prospective study was performed during 2011 at Rambam department of critical care medicine, on the influence of a simplified SDD protocol on the acquisition of AGNB infection in the ICU. The results show a significant reduction in blood stream infections and a change in the epidemiology of colonization of the respiratory tract - from resistant to sensitive bacteria. There was a concomitant reduction in the use of MDRO- targeted antibiotics.

The proposed multi-center study is based on this successful experience and will focus on the influence of a simplified SDD protocol on colonization and infection with MDROs in israeli ICUs where CREs are endemic.

Conditions

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Bacteremia Associated With Intravascular Line Ventilator Associated Pneumonia Bacteremia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Neomycin Colistin Nystatin Vancomycin

All participating study arm patients will receive SDD from admission to discharge according to the following plan:

ENTERAL MEDICATION (via feeding tube) x 4 times daily:

375 mg Neomycin 100 mg Colistin Sulphate

1 million units Nystatin \* 250 mg Vancomycin \*

Nystatin will be prescribed only if there is a positive sputum or urine culture for yeast or candida Vancomycin will be prescribed only in case of a positive screen or culture for MRSA

Group Type EXPERIMENTAL

Neomycin Colistin Nystatin Vancomycin

Intervention Type DRUG

All participating study arm patients will receive SDD from admission to discharge

Control

No SDD given for 1 year Screening performed as in intervention arm

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Neomycin Colistin Nystatin Vancomycin

All participating study arm patients will receive SDD from admission to discharge

Intervention Type DRUG

Other Intervention Names

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375 mg Neomycin 100 mg Colistin Sulphate 1 million units Nystatin * 250 mg Vancomycin *

Eligibility Criteria

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Inclusion Criteria

1. Expected to be in the ICU \> 72 hours
2. Has an enteral feeding tube and can receive enteral medication
3. Has a tracheal tube

Exclusion Criteria

1. Pt. is moribund - not expected to survive \> 28 days
2. Pt. or legal representative refuse to participate
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rambam Health Care Campus

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yaron P Bar-Lavie, M.D.

Role: STUDY_CHAIR

Rambam Health Care Campus, Haifa, Israel

Mical Paul, Prof.

Role: PRINCIPAL_INVESTIGATOR

Rambam Health Care Campus, Haifa, Israel

Locations

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Rambam Health Care Campus

Haifa, , Israel

Site Status

Countries

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Israel

Central Contacts

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Yaron P Bar-Lavie, M.D.

Role: CONTACT

++972-50-206-2027

Mical Paul, Prof.

Role: CONTACT

++972-50-206-2140

Facility Contacts

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Yaron P Bar-Lavie, M.D.

Role: primary

++972-50-206-2027

Mical Paul, Prof.

Role: backup

++972-50-206-2140

References

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de Jonge E, Schultz MJ, Spanjaard L, Bossuyt PM, Vroom MB, Dankert J, Kesecioglu J. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet. 2003 Sep 27;362(9389):1011-6. doi: 10.1016/S0140-6736(03)14409-1.

Reference Type BACKGROUND
PMID: 14522530 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19118302 (View on PubMed)

de Smet AM, Kluytmans JA, Blok HE, Mascini EM, Benus RF, Bernards AT, Kuijper EJ, Leverstein-van Hall MA, Jansz AR, de Jongh BM, van Asselt GJ, Frenay IH, Thijsen SF, Conijn SN, Kaan JA, Arends JP, Sturm PD, Bootsma MC, Bonten MJ. Selective digestive tract decontamination and selective oropharyngeal decontamination and antibiotic resistance in patients in intensive-care units: an open-label, clustered group-randomised, crossover study. Lancet Infect Dis. 2011 May;11(5):372-80. doi: 10.1016/S1473-3099(11)70035-4. Epub 2011 Mar 21.

Reference Type BACKGROUND
PMID: 21420908 (View on PubMed)

Schultz MJ, Haas LE. Antibiotics or probiotics as preventive measures against ventilator-associated pneumonia: a literature review. Crit Care. 2011;15(1):R18. doi: 10.1186/cc9963. Epub 2011 Jan 13.

Reference Type BACKGROUND
PMID: 21232110 (View on PubMed)

van Saene HK, Petros AJ, Ramsay G, Baxby D. All great truths are iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth. Intensive Care Med. 2003 May;29(5):677-90. doi: 10.1007/s00134-003-1722-2. Epub 2003 Apr 10.

Reference Type BACKGROUND
PMID: 12687326 (View on PubMed)

Silvestri L, van Saene HK, Milanese M, Gregori D, Gullo A. Selective decontamination of the digestive tract reduces bacterial bloodstream infection and mortality in critically ill patients. Systematic review of randomized, controlled trials. J Hosp Infect. 2007 Mar;65(3):187-203. doi: 10.1016/j.jhin.2006.10.014. Epub 2007 Jan 22.

Reference Type BACKGROUND
PMID: 17244516 (View on PubMed)

Other Identifiers

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NIHP Israel

Identifier Type: OTHER

Identifier Source: secondary_id

0401-12-RMB CTIL

Identifier Type: -

Identifier Source: org_study_id

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