Bacteremia Associated With Intravascular LinePhase 2/3SDDICUNCT01798537
Simplified Selective Digestive Tract Decontamination for the Prevention of Intensive Care Unit Acquired Infections
A Phase 2/3 study testing Neomycin Colistin Nystatin Vancomycin in people with Bacteremia Associated With Intravascular Line and Ventilator Associated Pneumonia, run by Rambam Health Care Campus at 1 site in Israel.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacteremia Associated With Intravascular Line, Ventilator Associated Pneumonia, Bacteremia
- What is being tested?
- Neomycin Colistin Nystatin Vancomycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,400 participants
- Where
- 1 siteIsrael
- Study dates
- Jun 2013to Jul 2015
- Phase
- Phase 2/3
- 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
Who may be able to join
- Expected to be in the ICU > 72 hours
- Has an enteral feeding tube and can receive enteral medication
- Has a tracheal tube
Who cannot join
- Pt. is moribund - not expected to survive > 28 days
- Pt. or legal representative refuse to participate
Trial locations and contacts
1 site in 1 country.
Israel1 site
Rambam Health Care Campus
Haifa, 31096
Yaron P Bar-Lavie, M.D., ++972-50-206-2027, y_barlavie@rambam.health.gov.il
Mical Paul, Prof., ++972-50-206-2140, m_paul@rambam.health.gov.il
About this study
Official title: Simplified Selective Digestive Tract Decontamination for the Prevention of ICU Infections in the Setting of High-level Antibiotic Resistance
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.
Read the detailed description
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
- Bacteremia Associated With Intravascular Line, Ventilator Associated Pneumonia, Bacteremia
- Being tested
- Neomycin Colistin Nystatin Vancomycin
- Medical subject headings
- Pneumonia, Ventilator-Associated, Bacteremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neomycin Colistin Nystatin VancomycinDrug
Also called 375 mg Neomycin, 100 mg Colistin Sulphate, 1 million units Nystatin *, 250 mg Vancomycin *
All participating study arm patients will receive SDD from admission to discharge
| Study group | Role | What they receive |
|---|---|---|
| Neomycin Colistin Nystatin Vancomycin | Experimental | 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 Receives: Drug: Neomycin Colistin Nystatin Vancomycin |
| Control | No intervention | No SDD given for 1 year Screening performed as in intervention arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Intensive care acquired infections per 1000 device days
A simplified graded SDD protocol combined with rigorous bi-weekly screening and appropriate bacterial prophylaxis, will lead to a reduction in the acquisition of central venous line blood-stream infections and to a reduction in ventilator associated pneumonia. There will be no concomitant rise in gram-positive or fungal infection or a surgency of new resistance patterns.
Measured: two years
Secondary outcomes (1)
The effect of SDD on the morbidity and mortality from MDRO on israeli ICU patients.
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2013 (estimated)
- Study startJun 2013
- Primary completionJul 2015 (estimated)
- Study completionJul 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Bacteremia Associated With Intravascular LineStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 2,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yaron P Bar-Lavie, M.D., Study chair, Rambam Health Care Campus, Haifa, IsraelMical Paul, Prof., Principal investigator, Rambam Health Care Campus, Haifa, Israel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01798537
- Sponsor's protocol ID
- 0401-12-RMB CTIL
- Other IDs
- NIHP Israel
- Acronym
- SDDICU
- Status last verified
- Feb 2013
- First submitted
- 17 Feb 2013
- Last updated
- 26 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 14522530de 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.
PubMed 19118302de 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.
PubMed 21420908Schultz 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.
PubMed 21232110van 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.
PubMed 12687326Silvestri 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.
PubMed 17244516
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Simplified Selective Digestive Tract Decontamination for the Prevention of ICU Infections in the Setting of High-level Antibiotic Resistance
- ClinicalTrials.gov ID
- NCT01798537
- Acronym / sponsor ID
- SDDICU / 0401-12-RMB CTIL
- Conditions
- Bacteremia Associated With Intravascular Line, Ventilator Associated Pneumonia, Bacteremia
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,400 participants (estimated)
- Lead sponsor
- Rambam Health Care CampusUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Jul 2015 (estimated)
- Study completion
- Jul 2015 (estimated)
- First posted
- 26 Feb 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.
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
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neomycin Colistin Nystatin Vancomycin | Experimental | Drug: Neomycin Colistin Nystatin VancomycinAll 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 |
| Control | No intervention | –No SDD given for 1 year Screening performed as in intervention arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Expected to be in the ICU > 72 hours
- Has an enteral feeding tube and can receive enteral medication
- Has a tracheal tube
Key exclusion criteria (2 listed)
- Pt. is moribund - not expected to survive > 28 days
- Pt. or legal representative refuse to participate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neomycin Colistin Nystatin VancomycinAlso: 375 mg Neomycin, 100 mg Colistin Sulphate, 1 million units Nystatin *, 250 mg Vancomycin *All participating study arm patients will receive SDD from admission to discharge | Drug | Neomycin Colistin Nystatin Vancomycin |
Primary outcome
Number of Intensive care acquired infections per 1000 device days
Time frame: two years
A simplified graded SDD protocol combined with rigorous bi-weekly screening and appropriate bacterial prophylaxis, will lead to a reduction in the acquisition of central venous line blood-stream infections and to a reduction in ventilator associated pneumonia. There will be no concomitant rise in gram-positive or fungal infection or a surgency of new resistance patterns.
1 secondary outcome
The effect of SDD on the morbidity and mortality from MDRO on israeli ICU patients.
Time frame: two years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2013.
- Background: PubMed 14522530de 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.
- Background: PubMed 19118302de 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.
- Background: PubMed 21420908de 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.
- Background: PubMed 21232110Schultz 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.
- Background: PubMed 12687326van 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.
- Background: PubMed 17244516Silvestri 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.
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.
Yaron P Bar-Lavie, M.D. study chair
Rambam Health Care Campus, Haifa, Israel
Mical Paul, Prof. principal investigator
Rambam Health Care Campus, Haifa, Israel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Neomycin Colistin Nystatin Vancomycin in people with Bacteremia Associated With Intravascular Line and Ventilator Associated Pneumonia, run by Rambam Health Care Campus at 1 site in Israel.
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 3 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 26 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yaron P Bar-Lavie, M.D. (++972-50-206-2027, y_barlavie@rambam.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Intensive care acquired infections per 1000 device days (time frame: two years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01798537, which also lists 6 linked publications.
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 26 Feb 2013.