Patients with low risk neutropenic sepsis Infections and Infestations Sepsis, unspecified
Conditions
Interventions
Intervention arm:
Switch to oral ciprofloxacin & co-amoxiclav, 12-24 hours after starting intravenous therapy with standard dose piperacillin/tazobactam or meropenem for at least 5 days total antibiot
Sponsors
Belfast Health and Social Care Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 05/04/2019: 1. Age over 16 years 2. Receiving SACT for a diagnosis of cancer 3. Started on empirical intravenous piperacillin/tazobactam or meropenem, for suspected NS, for less than 24 hours. Patients who have been started on additional antimicrobial drugs (eg. gentamicin or teicoplanin) are eligible provided the physician in charge of their care is willing to stop this additional antimicrobial at the time of enrolment. 4. Absolute neutrophil count =1.0x109/L with either a temperature of at least 38oC or other signs or symptoms consistent with clinically significant sepsis e.g. hypothermia. Self-measurement at home or earlier hospital assessment of temperature are acceptable provided this is documented in medical notes and is within 24 hours prior to IV antibiotic administration. 5. Expected duration of neutropenia 38oC) 4. Neutropenia (absolute neutrophil count =0.5x109/L) within the 24 hours prior to randomisation 5. Received intravenous antibiotics (piperacillin/tazobactam or meropenem) for less than 24 hours 6. Expected duration of neutropenia <7 days 7. Low risk of complications using a validated risk score (MASCC score =21) 8. Able to maintain adequate oral intake and take oral medication 9. Adequate hepatic (AST and/or ALT <2.5xULN, or <5xULN if hepatic metastases) and renal function (serum creatinine <3xULN) within 24 hours prior to randomisation 10. Physician in charge of care willing to follow either the intervention or standard care protocol per randomisation, at enrolment, including not treating with colony stimulating factor (CSF)
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 05/04/2019: 1. Underlying diagnosis of acute leukaemia or haematopoietic stem cell transplant 2. Hypotension (systolic pressure 40mmHg from known baseline on >1 measurement) within the 24 hours prior to randomisation 3. Prior allergy, serious adverse reaction, or contra-indication to any study drug 4. Enrolled in this trial with prior episode of neutropenic sepsis 5. Previously documented as being colonised with an organism resistant to a study drug regimen e.g. MRSA 6. Localising signs of severe infection (pneumonia, soft tissue infection, central-venous access device infection, presence of purulent collection) 7. Patients unable to provide informed consent 8. Pregnant women, women who have not yet reached the menopause (no menses for = 12 months without an alternative medical cause) who test positive for pregnancy, are unwilling to take a pregnancy test prior to trial entry or are unwilling to undertake adequate precautions to prevent pregnancy for the duration of the trial 9. Breastfeeding women Previous exclusion criteria: 1. Underlying diagnosis of acute leukaemia or haematopoietic stem cell transplant 2. Hypotension (systolic pressure <90 mmHg) within the 24 hours prior to randomisation 3. Prior allergy, serious adverse reaction, or contra-indication to any study drug 4. Treatment with fluoroquinolone or penicillin antibiotics in the preceding 14 days 5. Enrolled in this trial with prior episode of neutropenic sepsis 6. Previously documented as being colonised with an organism resistant to a study drug regimen e.g. MRSA 7. Localising signs of severe infection (pneumonia, soft tissue infection, central-venous access device infection, presence of purulent collection) 8. Patients unable to provide informed consent 9. Pregnant women, women who have not yet reached the menopause (no menses for = 12 months without an alternative medical cause) who test positive for pregnancy, are unwilling to take a pregnancy test prior to trial entry or are unwilling to undertake adequate precautions to prevent pregnancy for the duration of the trial 10. Breastfeeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment failure defined as one or more of the following criteria are met by day 14: 1. Persistence or recurrence of fever (temperature >38oC) after 72hrs of starting intravenous antibiotic treatment 2. Physician-directed escalation from protocol antibiotic treatment 3. Re-admission to hospital (related to infection or antibiotic treatment) 4. Critical care admission 5. Death | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Change in health-related quality of life EQ-5D-5L at baseline and 14 days 2. Cost-effectiveness of early switch compared to standard care at 14 days 3. Time to resolution of fever from initial IV antibiotic administration 4. Adverse events related to antibiotics 5. Duration of hospital admission 6. Readmission to hospital within 28 days 7. Death within 28 days 8. Adjustment to the subsequent scheduled cycle of chemotherapy within 28 days 9. Patient preferences for antibiotic treatment Exploratory objective: Identification of potential biomarkers for risk stratification in neutropenic sepsis | — |
Countries
England, Northern Ireland, United Kingdom, Wales
Contacts
Public ContactColette Jackson
Outcome results
None listed