Gram Negative Bacteremia Clinical Trial
Official title:
Duration of Antibiotics for the Treatment of Gram-negative Bacilli Bacteremia - a Randomized Controlled Trial
| NCT number | NCT01737320 |
| Other study ID # | 0258-12-RMC |
| Secondary ID | |
| Status | Completed |
| Phase | N/A |
| First received | |
| Last updated | |
| Start date | January 2013 |
| Est. completion date | March 4, 2018 |
| Verified date | April 2019 |
| Source | Rabin Medical Center |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 604 |
| Est. completion date | March 4, 2018 |
| Est. primary completion date | March 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - 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: 1. Primary bacteremia / unknown source 2. Urinary tract 3. Abdominal 4. Respiratory tract 5. Central venous catheter(CVC), when the catheter was removed before randomization 6. Skin and soft tissue, including surgical site infection Exclusion Criteria: 1. Gram-negative bacteremia due to specific infections as detailed here: 1. Endocarditis / endovascular infections 2. Necrotizing fasciitis 3. Osteomyelitis 4. Abdominal abscesses and other unresolved abdominal sources requiring surgical intervention (e.g., cholecystitis) 5. Central nervous system infections 6. Empyema 7. 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. 2. 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). 3. Specific pathogens including: 1. Salmonella spp. 2. Brucella spp. 4. Immunosuppression, including: 1. HIV infection 2. Hematopoietic stem-cell transplantation 3. 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. 5. Clinical instability during the 48 hours before randomization, defined as mean blood pressure<60 mmHg despite adequate fluid resuscitation or vasopressors support. 6. 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. 7. 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. 8. 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. 9. Previous enrollment in this trial 10. Concurrent participation in another clinical trial |
| Country | Name | City | State |
|---|---|---|---|
| Israel | Rambam Health Care Center | Haifa | |
| Israel | Rabin medical center, Beilinson Hospital | Petah Tikvah | |
| Italy | Policlinico di Modena, Italy | Modena | Emilia Romagna |
| Lead Sponsor | Collaborator |
|---|---|
| Rabin Medical Center |
Israel, Italy,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | composite of the following | The primary outcome is a composite of the following outcome measures | Until day 90 after randomization | |
| Primary | All -cause mortality | All- cause mortality | Until day 90 after randomization | |
| Primary | 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 |
Until day 90 after randomization | |
| Primary | 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. |
Until day 90 after randomization | |
| Secondary | Clostridium difficile associated diarrhea | Clostridium difficile associated diarrhea | Until day 30 after randomization | |
| Secondary | 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. | Until day 30 after randomization | |
| Secondary | Carriage of carbapenem resistant Klebsiella pneumonia. | Carriage of carbapenem resistant Klebsiella pneumonia (screened routinely) | Until day 30 after randomization | |
| Secondary | Total in hospital days | Total in hospital days within 30 and 90 days | Until day 90 after randomization. | |
| Secondary | Total antibiotic days | Total antibiotic days | Until day 30 after randomization | |
| Secondary | 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 |
Until day 30 after randomization | |
| Secondary | 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 | Until day 90 after randomization | |
| Secondary | Number of hospital re-admissions | Number of hospital re-admissions until day 90 | Until day 90 after randomization | |
| Secondary | Functional capacity and time to return to baseline activity | Functional capacity and time to return to baseline activity | Until day 30 after randomization |