Gram Negative BacteremiaNCT01737320
Duration of Antibiotics for the Treatment of Gram-negative Bacilli Bacteremia
A study testing short-course antibiotic treatment and accepted prolonged antibiotic treatment in people with Gram Negative Bacteremia, run by Rabin Medical Center at 3 sites in 2 countries.
Trial summary
The investigators plan an open label randomized controlled trial to compare short-course antibiotic therapy (<=7 days) versus longer treatment (>7 days). The investigators will include hospitalized patients with gram-negative bacteremia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gram Negative Bacteremia
- What is being tested?
- short-course antibiotic treatment and accepted prolonged antibiotic treatment
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 604 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Jan 2013to 4 Mar 2018
- Phase
- Interventional
- 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
- patients with gram-negative aerobic bacilli bacteremia, defined as growth of a single gram-negative microorganism in one or more blood cultures, associated with evidence of infection (hyper- or hypothermia, a localized infection, sepsis or septic shock).
- We will include patients receiving appropriate antibiotic treatment for 7 days and are afebrile / not hypothermic for the last 48 hours. Both community and hospital acquired gram-negative bacteremias will be included, regardless of antibiotic susceptibility patterns. We will allow the inclusion of patients receiving less than 7 days if clinically stable and discharge from hospital is considered. We will then recruit the patient before discharge, if stable at least for 48 hours before randomization.
- We will include the following sources of bacteremia:
- Primary bacteremia / unknown source
- Urinary tract
- Abdominal
Show all 9Show fewer
- Respiratory tract
- Central venous catheter(CVC), when the catheter was removed before randomization
- Skin and soft tissue, including surgical site infection
Who cannot join
- Gram-negative bacteremia due to specific infections as detailed here:
- Endocarditis / endovascular infections
- Necrotizing fasciitis
- Osteomyelitis
- Abdominal abscesses and other unresolved abdominal sources requiring surgical intervention (e.g., cholecystitis)
- Central nervous system infections
Show all 22Show fewer
- Empyema
- CVC- related or CVC-associated bloodstream infections when the catheter is retained. We will permit the inclusion of patients with retained CVCs in whom the source of the bacteremia is not the CVC.
- Polymicrobial growth in blood cultures involving gram-positive or anaerobes in addition to gram-negatives (defined as either growth of two or more different species of microorganisms in the same blood culture, or growth of different species in two or more separate blood cultures within the same episode (< 48 h) and with clinical or microbiological evidence of the same source).
- Specific pathogens including:
- Salmonella spp.
- Brucella spp.
- Immunosuppression, including:
- HIV infection
- Hematopoietic stem-cell transplantation
- Neutropenia on day of randomization or in the 48 hours prior to randomization. Patients with neutropenic fever at presentation that are afebrile and non-neutropenic in the 48 hours before randomization will be included.
- Clinical instability during the 48 hours before randomization, defined as mean blood pressure<60 mmHg despite adequate fluid resuscitation or vasopressors support.
- Repeated positive blood cultures for the same organism separated by at least 24 hours, regardless of antibiotic treatment. Patients with repeated isolates on the first 24 hours will be included.
- Uncontrolled focus of infection: e.g. an abscess that was not drained sufficiently; non-drained moderate to severe hydronephrosis in a patient with bacteremia of urinary source; deep seated intra-abdominal infections that were not drained properly.
- Fever > 38.0C measured at least twice in the 48 h prior to recruitment; or > 38.5C once during the 48 h; or hypothermia <35.5C measured once during the 48 h.
- Previous enrollment in this trial
- Concurrent participation in another clinical trial
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Israel2 sites
Rambam Health Care Center
Haifa
Rabin medical center, Beilinson Hospital
Petah Tikvah
About this study
Official title: Duration of Antibiotics for the Treatment of Gram-negative Bacilli Bacteremia - a Randomized Controlled Trial
The investigators plan an open label randomized controlled trial to compare short-course antibiotic therapy (<=7 days) versus longer treatment (>7 days). The investigators will include hospitalized patients with gram-negative bacteremia. The investigators primary objective is to investigate the safety and efficacy of short-course antibiotics.
- Conditions
- Gram Negative Bacteremia
- Being tested
- short-course antibiotic treatment, accepted prolonged antibiotic treatment
- Keywords
- gram negative bacteremia, Duration of antibiotic treatment, safety, efficacy, short-course
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
short-course antibiotic treatmentDrug
On day 7 of appropriate intravenous or oral antibiotic treatment for the bacteremic episode (day 1 is the first day of appropriate antibiotic therapy), patients will be randomized to:
- Intervention group - antibiotic treatment stopped on day 7
- Control group - antibiotic treatment continued for 14 days according to accepted hospital local guidelines.
accepted prolonged antibiotic treatmentDrug
| Study group | Role | What they receive |
|---|---|---|
| short-course | Experimental | antibiotic treatment stopped on day 7 if the patient has been afebrile for 48 hours and clinically stable. Continued hospitalization will be left to the discretion of the treating physician. Antibiotics will be restarted if fever recurs in at least 2 consecutive measurements above 38 or in cases of clinically or microbiologically documented infections. Receives: Drug: short-course antibiotic treatment |
| accepted prolonged antibiotic treatment | Active comparator | antibiotic treatment continued for 14 days according to accepted hospital local guidelines. Duration of hospital stay will also be left to the discretion of the treating physician.
Type of empiric antibiotic treatment and later, specific antibiotic treatment, will be chosen by the treating physicians in consultation with the infectious diseases unit.
The decision on timing of switch to oral antibiotic therapy will also be left to the discretion of the treating physician. Receives: Drug: accepted prolonged antibiotic treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
composite of the following
The primary outcome is a composite of the following outcome measures
Measured: Until day 90 after randomization
All -cause mortality
All- cause mortality
Measured: Until day 90 after randomization
Treatment Failure
Failure including any of the following:
- Relapse: a recurrent bacteraemia due to the same microorganism occurring from day of randomization and until day 9013
- Local suppurative complication that was not present at infection onset (e.g. renal abscess in pyelonephritis, empyema in pneumonia)
- Distant complications of initial infection, defined by growth of the same bacteria as in the initial bacteremia
Measured: Until day 90 after randomization
Hospital re-admissions or extended hospitalization
We will define re-admission as a new hospitalization for any cause occurring more than14 days from start of appropriate antibiotic treatment. Patients hospitalized after day 14 (were never discharged or 7-day regimen who were readmitted between days 7-14) will be counted as failures for this outcome.
We will define re-admission as a new hospitalization for any cause occurring more than14 days from start of appropriate antibiotic treatment. Patients hospitalized after day 14 (were never discharged or 7-day regimen who were readmitted between days 7-14) will be counted as failures for this outcome.
Measured: Until day 90 after randomization
Secondary outcomes (9)
Clostridium difficile associated diarrhea
Clostridium difficile associated diarrhea
Measured: Until day 30 after randomization
Development of Antibiotic resistance
Development of resistance, defined as clinical isolates resistant to antibiotics previously used in the bacteremia episode. Surveillance sampling will not be conducted.
Measured: Until day 30 after randomization
Carriage of carbapenem resistant Klebsiella pneumonia.
Carriage of carbapenem resistant Klebsiella pneumonia (screened routinely)
Measured: Until day 30 after randomization
Total in hospital days
Total in hospital days within 30 and 90 days
Measured: Until day 90 after randomization.
Total antibiotic days
Total antibiotic days
Measured: Until day 30 after randomization
Adverse events
- Any diarrhea
- Liver function test abnormalities, defined as elevated bilirubin x 1.5 of upper limit of normal or transaminases x 2.5 of upper limit of normal
- Antibiotic rash
- Acute kidney injury - defined according to RIFLE criteria as increased creatinine level x 1.5 from baseline or glomerular filtration rate (GFR) decrease >25% or urine output of <0.5 ml/kg/h for 6 hours22
Measured: Until day 30 after randomization
Infection caused by other than gram-negative bacteremia
Development of either clinically or microbiologically documented infection other than gram-negative bacteremia. We will use the 2008 CDC/NHSN surveillance definitions of health-care associated infections for bacterial infections
Measured: Until day 90 after randomization
Number of hospital re-admissions
Number of hospital re-admissions until day 90
Measured: Until day 90 after randomization
Functional capacity and time to return to baseline activity
Functional capacity and time to return to baseline activity
Measured: Until day 30 after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2012 (estimated)
- Study startJan 2013
- Primary completionMar 2018
- Study completion4 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gram Negative BacteremiaStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 604 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rabin Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, dafna yahav, Rabin Medical Center
- Investigators
- Dafna Yahav, MD, Principal investigator, Rabin Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01737320
- Sponsor's protocol ID
- 0258-12-RMC
- Status last verified
- Apr 2019
- First submitted
- 14 Nov 2012
- Last updated
- 9 Apr 2019
- Results posted
- No
Publications
Yahav D, Franceschini E, Koppel F, Turjeman A, Babich T, Bitterman R, Neuberger A, Ghanem-Zoubi N, Santoro A, Eliakim-Raz N, Pertzov B, Steinmetz T, Stern A, Dickstein Y, Maroun E, Zayyad H, Bishara J, Alon D, Edel Y, Goldberg E, Venturelli C, Mussini C, Leibovici L, Paul M; Bacteremia Duration Study Group. Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial. Clin Infect Dis. 2019 Sep 13;69(7):1091-1098. doi: 10.1093/cid/ciy1054.
PubMed 30535100
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Duration of Antibiotics for the Treatment of Gram-negative Bacilli Bacteremia - a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01737320
- Acronym / sponsor ID
- 0258-12-RMC
- Conditions
- Gram Negative Bacteremia
- Keywords
- gram negative bacteremia, Duration of antibiotic treatment, safety, efficacy, short-course
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 604 participants (actual)
- Lead sponsor
- Rabin Medical CenterUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Mar 2018 (actual)
- Study completion
- 4 Mar 2018 (actual)
- First posted
- 29 Nov 2012 (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.
The investigators plan an open label randomized controlled trial to compare short-course antibiotic therapy (<=7 days) versus longer treatment (>7 days). The investigators will include hospitalized patients with gram-negative bacteremia. The investigators primary objective is to investigate the safety and efficacy of short-course antibiotics.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| short-course | Experimental | Drug: short-course antibiotic treatmentantibiotic treatment stopped on day 7 if the patient has been afebrile for 48 hours and clinically stable. Continued hospitalization will be left to the discretion of the treating physician. Antibiotics will be restarted if fever recurs in at least 2 consecutive measurements above 38 or in cases of clinically or microbiologically documented infections. |
| accepted prolonged antibiotic treatment | Active comparator | Drug: accepted prolonged antibiotic treatmentantibiotic treatment continued for 14 days according to accepted hospital local guidelines. Duration of hospital stay will also be left to the discretion of the treating physician. Type of empiric antibiotic treatment and later, specific antibiotic treatment, will be chosen by the treating physicians in consultation with the infectious diseases unit. The decision on timing of switch to oral antibiotic therapy will also be left to the discretion of the treating physician. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- patients with gram-negative aerobic bacilli bacteremia, defined as growth of a single gram-negative microorganism in one or more blood cultures, associated with evidence of infection (hyper- or hypothermia, a localized infection, sepsis or septic shock).
- We will include patients receiving appropriate antibiotic treatment for 7 days and are afebrile / not hypothermic for the last 48 hours. Both community and hospital acquired gram-negative bacteremias will be included, regardless of antibiotic susceptibility patterns. We will allow the inclusion of patients receiving less than 7 days if clinically stable and discharge from hospital is considered. We will then recruit the patient before discharge, if stable at least for 48 hours before randomization.
- Primary bacteremia / unknown source
- Urinary tract
- Abdominal
Key exclusion criteria (22 listed)
- Gram-negative bacteremia due to specific infections as detailed here:
- Polymicrobial growth in blood cultures involving gram-positive or anaerobes in addition to gram-negatives (defined as either growth of two or more different species of microorganisms in the same blood culture, or growth of different species in two or more separate blood cultures within the same episode (< 48 h) and with clinical or microbiological evidence of the same source).
- Specific pathogens including:
- Immunosuppression, including:
- Clinical instability during the 48 hours before randomization, defined as mean blood pressure<60 mmHg despite adequate fluid resuscitation or vasopressors support.
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 |
|---|---|---|
| short-course antibiotic treatmentOn day 7 of appropriate intravenous or oral antibiotic treatment for the bacteremic episode (day 1 is the first day of appropriate antibiotic therapy), patients will be randomized to: 1. Intervention group - antibiotic treatment stopped on day 7 2. Control group - antibiotic treatment continued for 14 days according to accepted hospital local guidelines. | Drug | short-course |
| accepted prolonged antibiotic treatment | Drug | accepted prolonged antibiotic treatment |
Primary outcome
composite of the following
Time frame: Until day 90 after randomization
The primary outcome is a composite of the following outcome measures
All -cause mortality
Time frame: Until day 90 after randomization
All- cause mortality
Treatment Failure
Time frame: Until day 90 after randomization
Failure including any of the following: 1. Relapse: a recurrent bacteraemia due to the same microorganism occurring from day of randomization and until day 9013 2. Local suppurative complication that was not present at infection onset (e.g. renal abscess in pyelonephritis, empyema in pneumonia) 3. Distant complications of initial infection, defined by growth of the same bacteria as in the initial bacteremia
Hospital re-admissions or extended hospitalization
Time frame: Until day 90 after randomization
We will define re-admission as a new hospitalization for any cause occurring more than14 days from start of appropriate antibiotic treatment. Patients hospitalized after day 14 (were never discharged or 7-day regimen who were readmitted between days 7-14) will be counted as failures for this outcome. We will define re-admission as a new hospitalization for any cause occurring more than14 days from start of appropriate antibiotic treatment. Patients hospitalized after day 14 (were never discharged or 7-day regimen who were readmitted between days 7-14) will be counted as failures for this outcome.
9 secondary outcomes
Clostridium difficile associated diarrhea
Time frame: Until day 30 after randomization
Development of Antibiotic resistance
Time frame: Until day 30 after randomization
Carriage of carbapenem resistant Klebsiella pneumonia.
Time frame: Until day 30 after randomization
Total in hospital days
Time frame: Until day 90 after randomization.
Total antibiotic days
Time frame: Until day 30 after randomization
Adverse events
Time frame: Until day 30 after randomization
Infection caused by other than gram-negative bacteremia
Time frame: Until day 90 after randomization
Number of hospital re-admissions
Time frame: Until day 90 after randomization
Functional capacity and time to return to baseline activity
Time frame: Until day 30 after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2019.
- Derived from this study: PubMed 30535100Yahav D, Franceschini E, Koppel F, Turjeman A, Babich T, Bitterman R, Neuberger A, Ghanem-Zoubi N, Santoro A, Eliakim-Raz N, Pertzov B, Steinmetz T, Stern A, Dickstein Y, Maroun E, Zayyad H, Bishara J, Alon D, Edel Y, Goldberg E, Venturelli C, Mussini C, Leibovici L, Paul M; Bacteremia Duration Study Group. Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial. Clin Infect Dis. 2019 Sep 13;69(7):1091-1098. doi: 10.1093/cid/ciy1054.
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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.
Dafna Yahav, MD principal investigator
Rabin Medical Center
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing short-course antibiotic treatment and accepted prolonged antibiotic treatment in people with Gram Negative Bacteremia, run by Rabin Medical Center at 3 sites in 2 countries.
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 9 inclusion and 22 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: finished, as of the sponsor's last update on 9 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Israel, Italy. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
composite of the following (time frame: Until day 90 after randomization). The study lists 4 primary outcomes in all. 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 NCT01737320, which also lists 1 linked publication.
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 9 Apr 2019.