Early switch to oral antibiotics in patients with low risk neutropenic sepsis
| ISRCTN | ISRCTN84288963 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN84288963 |
| EudraCT/CTIS number | 2015-002830-35 |
| Secondary identifying numbers | HTA 13/140/05; 15040RM-SS |
- Submission date
- 30/06/2015
- Registration date
- 01/07/2015
- Last edited
- 18/08/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Neutropenic sepsis is a potentially life-threatening complication of chemotherapy caused by a condition known as neutropenia, in which the number of white blood cells (called neutrophils) in the blood is low. Neutrophils help the body to fight infection. People receiving chemotherapy for cancer treatment can be at risk of neutropenic sepsis because these treatments can temporarily lower the number of neutrophils in the blood. There is universal agreement that prompt antibiotic treatment is required, but less agreement about how best to manage patients thereafter. This study aims to find out whether changing from intravenous antibiotics (administered into a vein) to oral antibiotics on the first day of treatment is clinically and cost-effective in comparison with longer duration intravenous antibiotics in patients at low risk of complications.
Who can participate?
Patients undergoing chemotherapy who are admitted to hospital with low risk neutropenic sepsis.
What does the study involve?
Once you have consented you will undergo the required study tests and provide a blood sample, have your medical history and medications checked, and complete a short questionnaire. You will then be allocated to one of two groups. One group will switch from intravenous to oral antibiotics 12-24 hours after commencing intravenous treatment, for a total of five days antibiotic treatment. The other group will receive standard care intravenous antibiotics for at least 48 hours then either continue or switch to oral antibiotics at the doctor’s discretion. After leaving hospital you will take any remaining antibiotic tablets and complete a progress diary , and a nurse will phone you to check on your progress and go through two short questionnaires.
What are the possible benefits and risks of participating?
The results of this study will inform the future medical care of patients who develop neutropenic sepsis while undergoing chemotherapy. The potential benefits of participating include fewer complications with intravenous lines, earlier discharge from hospital, higher quality of life and more cost-effective treatment. The potential risks of participating include antibiotic treatment failure, side effects of antibiotic treatment, and mild discomfort when providing one additional blood sample.
Where is the study run from?
Belfast City Hospital, The Freeman Hospital, Leicester Royal Infirmary and Velindre Hospital (UK).
When is the study starting and how long is it expected to run for?
The study is due to start recruiting at four pilot sites in November 2015. If successful the main study will recruit for an additional 30 months in 12 sites across the UK.
Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK).
Who is the main contact?
Dr Victoria Coyle
v.coyle@qub.ac.uk
Contact information
Scientific
Centre for Cancer Research and Cell Biology
Queens University Belfast
97 Lisburn Road
Belfast
BT9 7AE
United Kingdom
Public
NICTU
1st Floor Elliott Dynes Building
Royal Hospital Site
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
Scientific
Centre for Infection and Immunity
The Queen’s University of Belfast
Health Sciences Building
97 Lisburn Road
Belfast
BT9 7BL
United Kingdom
Study information
| Study design | Multi-centre interventional randomised controlled non-inferiority trial with allocation concealment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Study type | Participant information sheet |
| Scientific title | Early switch to oral antibiotic therapy in patients with low risk neutropenic sepsis: a randomised, controlled, non-inferiority trial with allocation concealment |
| Study acronym | EASI-SWITCH |
| Study hypothesis | Early switch to oral antibiotic therapy, 12-24 hours after intravenous antibiotic treatment commences in low risk cancer patients with neutropenic sepsis, is non-inferior to standard care. |
| Ethics approval(s) | Office for Research Ethics Committees Northern Ireland (ORECNI), 06/10/2015, ref: 15/NI/0161 |
| Condition | Patients with low risk neutropenic sepsis |
| Intervention | 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 antibiotic treatment. Standard care arm: Intravenous therapy with standard dose piperacilin/tazobactam or meropenem for at least 48 hours (later discontinuation +/- oral antibiotic switch at physician discretion). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Ciprofloxacin, co-amoxiclav |
| Primary outcome measure | 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 outcome measures | 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 |
| Overall study start date | 01/08/2015 |
| Overall study end date | 24/12/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | 230 |
| Total final enrolment | 129 |
| Participant 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 <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) |
| Participant 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 <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 |
| Recruitment start date | 01/11/2015 |
| Recruitment end date | 27/11/2019 |
Locations
Countries of recruitment
- England
- Northern Ireland
- United Kingdom
- Wales
Study participating centres
BT9 7AB
United Kingdom
CF14 2TL
United Kingdom
NE7 7DN
United Kingdom
LE1 5WW
United Kingdom
Sponsor information
Hospital/treatment centre
Research Governance
2nd Floor KEB Building
Grosvenor Road
Belfast
BT12 6BA
Northern Ireland
United Kingdom
"ROR" |
https://ror.org/02tdmfk69 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/09/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Final data analysis will take place in the third quarter of 2020 (June to Sept). The trial report and dissemination should take place in Sept 2020. The final study report will be provided by the Trial Statistician; it is anticipated that the study findings will be published in national and international peer review journals which will be led by the CI. Publications will be discussed at the TMG and will be considered on a case by case basis. This will secure a searchable compendium of these publications and make the results readily accessible to the public and health care professionals. In addition study findings may be presented at both national and international meetings and also to appropriate patient groups. Due to limited resources, it will not be possible to provide each patient with a personal copy of the results of the trial. However, upon request, patients involved in the trial will be provided with a lay summary of the principal study findings. The most significant results will be communicated to the public through press releases. An ongoing update of the trial will also be provided on the NICTU website. |
| IPD sharing plan | Requests for data sharing will be reviewed on an individual basis by the CI and TMG. The CI is Dr Victoria Coyle v.coyle@qub.ac.uk and Dr Ronan Mc Mullan is co-CI. ronan.mcmullan@belfasttrust.hscni.net. Please contact the TMG through the study email address: EASI-SWITCH@NICTU.HSCNI.NET |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version v8.0 | 05/04/2019 | No | No | |
| Protocol article | protocol | 27/05/2020 | 29/05/2020 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | 27/05/2020 | 18/08/2023 | No | Yes |
Additional files
- ISRCTN84288963_v8.0_21062018.docx.pdf
- Uploaded 05/04/2019
Editorial Notes
18/08/2023: Participant information sheet added.
29/05/2020: Publication reference added.
19/02/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/01/2020 to 27/11/2019.
2. The overall trial end date was changed from 01/02/2020 to 24/12/2019.
3. The total final enrolment number was added.
05/04/2019: The following changes were made to the trial record:
1. The target number of participants was changed from 628 to 230.
2. The recruitment end date was changed from 01/11/2018 to 01/01/2020.
3. The overall trial end date was changed from 01/05/2019 to 01/02/2020.
4. Publication and dissemination plan and IPD sharing statement added.
5. Uploaded protocol Version 8.0, 21 June 2018 (not peer reviewed).
6. The contact details and inclusion and exclusion criteria were updated.
24/03/2016: Ethics approval information added.
