Early switch to oral antibiotics in patients with low risk neutropenic sepsis
- Conditions
- Patients with low risk neutropenic sepsisInfections and InfestationsSepsis, unspecified
- Registration Number
- ISRCTN84288963
- Lead Sponsor
- Belfast Health and Social Care Trust (UK)
- Brief Summary
2020 Protocol article in https://pubmed.ncbi.nlm.nih.gov/32460818/ protocol (added 29/05/2020)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 129
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 <7 days
6. Low risk of complications using a validated risk score (MASCC score =21)
7. Able to maintain adequate oral intake and take oral medication
8. Adequate hepatic (AST &/or ALT <5xULN) and renal function (serum creatinine <3 x ULN) within the 24 hours prior to randomisation
9. 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). Prophylactic CSF is not an exclusion criterion if prescribed routinely as an integral component of a specific SACT regimen.
Previous inclusion criteria:
1. Age over 16 years
2. Receiving SACT for a diagnosis of cancer
3. Fever (temperature >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)
Current exclusion criteria as of 05/04/2019:
1. Underlying diagnosis of acute leukaemia or haematopoietic stem cell transplant
2. Hypotension (systolic pressure <90mmHg or reduction of >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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Treatment failure defined as one or more of the following criteria are met by day 14:<br>1. Persistence or recurrence of fever (temperature >38oC) after 72hrs of starting intravenous antibiotic treatment<br>2. Physician-directed escalation from protocol antibiotic treatment<br>3. Re-admission to hospital (related to infection or antibiotic treatment)<br>4. Critical care admission<br>5. Death
- Secondary Outcome Measures
Name Time Method 1. Change in health-related quality of life EQ-5D-5L at baseline and 14 days<br>2. Cost-effectiveness of early switch compared to standard care at 14 days<br>3. Time to resolution of fever from initial IV antibiotic administration<br>4. Adverse events related to antibiotics<br>5. Duration of hospital admission <br>6. Readmission to hospital within 28 days <br>7. Death within 28 days<br>8. Adjustment to the subsequent scheduled cycle of chemotherapy within 28 days<br>9. Patient preferences for antibiotic treatment <br><br>Exploratory objective:<br>Identification of potential biomarkers for risk stratification in neutropenic sepsis