Optimal Antibiotic Treatment of Moderate to Severe Bacterial Infections (CDSS)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2014 by Rabin Medical Center
Sponsor:
Information provided by (Responsible Party):
leibovici leonard, Rabin Medical Center
ClinicalTrials.gov Identifier:
NCT01338116
First received: March 30, 2011
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

Severe bacterial infections are associated with mortality of about 30%. Patients with moderate to severe bacterial infections given early and appropriate empirical antibiotic treatment are at a lesser risk for a fatal outcome, with odds ratios ranging from 1.6 to 6.9. However only about 2/3 of patients worldwide are given early and appropriate empirical antibiotic treatment. About 40% of patients treated with antibiotics are given superfluous treatment.

TREAT is a computerized decision support system for antibiotic treatment in inpatients with common bacterial infections. TREAT is based on a state of the art stochastic model of the domain (a causal probabilistic network) and uses a cost benefit model for antibiotic treatment, including costs assigned to future resistance. It was tested in a randomized controlled trial in 3 countries and shown to improve the percentage of appropriate empirical antibiotic treatment while at the same time reduce hospital stay and the use of broad-spectrum antibiotics. The main limitation of TREAT is inherent in the limited information available within hours of presentation.

A second attractive approach to improve antibiotic treatment is to use techniques that do not depend on cultures, and thus shorten the time to identification of the pathogen to a few hours only. The LightCycler® SeptiFast test from Roche performs in vitro nucleic acid amplification test for pathogens causing bloodstream infections.

The purpose of the clinical trial is to show that the combined system TREAT/PCR assays will improve the outcome of inpatients with moderate to severe bacterial infections, while at the same time reducing the use of broad-spectrum antibiotics, with no or little additional costs. A secondary objective will be to assess the sensitivity and specificity of whole blood PCR, using TREAT as the reference standard.


Condition Intervention Phase
Community-associated Infections
Health-care Acquired Infections
Nosocomial Infections
Other: antibiotic treatment of by TREAT/PCR
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Optimal Antibiotic Treatment of Moderate to Severe Bacterial Infections: Integration of PCR Technology and Medical Informatics/Artificial Intelligence

Resource links provided by NLM:


Further study details as provided by Rabin Medical Center:

Primary Outcome Measures:
  • Clinical success defined as 30-day survival and clinical stability on day 4 [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    patient alive at day 30; on day 4: no fever, no intra-tracheal tube, hemodynamic stable, no vasopressor support, empirical treatment appropriate (and thus not changed).


Secondary Outcome Measures:
  • Appropriate empirical antibiotic treatment [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Appropriateness of the antibiotic treatment given during the first 48 hours, before identification of the causative pathogen and its antibiotic susceptibilities

  • Survival [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Hospital stay [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Length of hospital stay

  • Antibiotic miuse of broad spectrum antibiotics and total costs of antibiotic treatment Superfluous antibiotic treatment [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Use of broad spectrum antibiotics and total costs of antibiotic treatment

  • Costs [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Costs incurred during hospital stay

  • Adverse events [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Allergy, nephrotoxicity, diarrhea, clostridium-difficile associated diarrhea and others


Estimated Enrollment: 600
Study Start Date: January 2015
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Management by TREAT/PCR
The data available at the time of patient recruitment will be entered into TREAT. TREAT will provide advice for the empirical antibiotic treatment and unless the caring physician can justify a deviation from this recommendation, TREAT's recommendation will be implemented (yes or no antibiotic treatment and type of antibiotic). TREAT will also recommend whether a blood sample for PCR should be obtained. Blood will be collected aseptically and the test will be performed once daily between 1000AM-1700PM (results available daily at 1700 PM). PCR results and a PCR-revised TREAT recommendation will be reported to the patient's physician in charge and treatment will be revised accordingly.
Other: antibiotic treatment of by TREAT/PCR
Management by TREAT/PCR. The data available at the time of patient recruitment will be entered into TREAT. TREAT will provide advice for the empirical antibiotic treatment and unless the caring physician can justify a deviation from this recommendation, TREAT's recommendation will be implemented (yes or no antibiotic treatment and type of antibiotic). TREAT will also recommend whether a blood sample for PCR should be obtained. Blood will be collected aseptically and the test will be performed once daily between 1000AM-1700PM (results available daily at 1700 PM). PCR results and a PCR-revised TREAT recommendation will be reported to the patient's physician in charge and treatment will be revised accordingly. On day 2, when results of blood cultures and other cultures become available TREAT will be re-consulted and will issue a new recommendation based on the full microbiological investigation (negative and positive results).
No Intervention: Usual management
Patients will be managed by physicians as in regular clinical practice.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

The rationale of the study will be to address patients for whom antibiotic treatment is, or should be, considered. Thus we will include consecutive patients detected in medical departments according to the following criteria:

  1. Patients from whom blood cultures were drawn or
  2. All patients for whom antibiotic treatment (but not prophylaxis or intra-peritoneal, inhalation or local antibiotics therapy ) is started within the last 96 days or
  3. Patients fulfilling the CDC diagnostic criteria for any infection (see appendix C) or
  4. Patients with temperature ≥38.3 measured orally (or 38 axillary or 38.5 rectal) on a single measurement or ≥38 / < 36 on at least 2 consecutive measurements separated at least 1 hr apart and one of the next criteria:

    (a) heart rate >90 beats/minute; (b) respiratory rate >20 breaths/minute or partial pressure of CO2 <32 mm Hg; and (c) white blood cell count >12,000/ L, <4000 L, or >10% immature (band) forms. or

  5. Patients with shock compatible with septic shock. As defined as hypotension (arterial blood pressure <90 mmHg systolic, or 40 mmHg less than patient's normal blood pressure) for at least 1 h despite adequate fluid resuscitation; Or Need for vasopressors to maintain systolic blood pressure >90 mmHg or mean arterial pressure >70 mmHg and a suspected source of infection.

Exclusion Criteria:

  1. HIV positive patients with opportunistic infection (suspected or proven)and / or AIDS defining illness in the last 6 months prior to data collection.
  2. Children<18 years.
  3. Suspected travel infections.
  4. Suspected tuberculosis.
  5. Pregnancy.
  6. We will exclude patients not able to sign informed consent or not having a legal guardian willing to do so.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01338116

Locations
Israel
Rabin Medical Center, Beilinson Hospital
Petah Tikvah, Israel, 49100
Sponsors and Collaborators
Rabin Medical Center
Investigators
Principal Investigator: Mical Paul, MD Rabin Medical Center
Principal Investigator: Leonard Leibovici, Prof Rabin Medical Center
  More Information

No publications provided

Responsible Party: leibovici leonard, Professor, Rabin Medical Center
ClinicalTrials.gov Identifier: NCT01338116     History of Changes
Other Study ID Numbers: 6036
Study First Received: March 30, 2011
Last Updated: March 25, 2014
Health Authority: Israel: Ministry of Health

Keywords provided by Rabin Medical Center:
computerized decision support system
PCR
antibiotic treatment

Additional relevant MeSH terms:
Bacterial Infections
Cross Infection
Infection
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents

ClinicalTrials.gov processed this record on August 19, 2014