Optimisation of perioperative cardiovascular management to improve surgical outcome II
ISRCTN | ISRCTN39653756 |
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DOI | https://doi.org/10.1186/ISRCTN39653756 |
Secondary identifying numbers | 011560 |
- Submission date
- 15/11/2016
- Registration date
- 23/11/2016
- Last edited
- 04/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Plain English summary of protocol
Background and study aims
Around 40,000 NHS patients aged 65 years and over undergo major planned gut surgery each year. After surgery, more than 12,000 patients develop an infection while they are in hospital (hospital acquired infection), and 3,600 die within 180 days. Patients who survive complications to leave hospital commonly suffer a loss of mobility, independence and reduced long-term survival. Hospital acquired infections in this patient group cost the NHS more than £80 million each year. Complications after surgery are more likely if patients receive too much or too little fluid through a drip. The use of small doses of drugs that increase heart function (inotropic drugs) is also important. Currently, the type and dose of these drug treatments is decided by a doctor based on opinion-based assessment of the patient. Advanced heart monitoring technologies may provide a more reliable guide to the use of these treatments. However, only one third of eligible patients currently receive this treatment because many doctors are concerned this approach is more aggressive and may therefore harm some patients by causing small heart attacks. Only a large study can resolve this uncertainty, to find out whether giving this treatment to all eligible patients is beneficial, or ineffective or harmful. The aim of this study is to find out the effect of this treatment on the number of patients who develop hospital acquired infection within 30 days after major planned gastrointestinal (gut) surgery.
Who can participate?
Adults over 65 years old who are undergoing planned major gastrointestinal (gut) surgery.
What does the study involve?
Participants are randomly allocated to one of two groups. Both treatments begin at the start of surgery and finish four hours after this has ended. The two treatments involve slightly different ways of deciding the amount of fluid and drugs given through a drip to improve heart function. If participants receive standard care the doctor uses measurements such as heart rate and blood pressure measurements to guide these treatments. If participants receive the new trial treatment doctors also measure the amount of blood the heart pumps each minute using an extra monitor. These extra measurements should help the doctor to decide how much fluid and drugs they should give to improve heart function. After the treatment is over, the study team reviews the participant’s medical records and may talk to the doctors to collect information about their recovery. Participants are also contacted by telephone in one month and again in six months’ time to ask some simple questions about their wellbeing. The phone call lasts for around five minutes. With the participant’s permission or if it is not possible to contact the participant, the study team may also contact their General Practitioner for further information.
What are the possible benefits and risks of participating?
There are no direct benefits of participating. Previous research suggests that the treatment we are investigating is very safe and should benefit most patients. However, there is a very small risk of a minor heart attack for some patients. For this reason, patients taking part in the study will be closely monitored throughout the trial period and, if necessary, the research team will make adjustments to the treatment to ensure patient safety.
Where is the study run from?
Hospitals in Australia, Canada, Germany, Spain, Sweden, United Kingdom and United States of America.
When is the study starting and how long is it expected to run for?
August 2016 to March 2023
Who is funding the study?
1. National Institute for Health Research (UK)
2. Edwards Lifesciences Corporation (UK)
Who is the main contact?
1. Dr Priyanthi Dias (scientific and public)
p.dias@qmul.ac.uk
Contact information
Scientific
Adult Critical Care Research
Room 14 Central Tower
The Royal London Hospital
Whitechapel
London
E1 1FR
United Kingdom
0000-0003-1740-6165 | |
Phone | +44 (0)20 3594 0349 |
p.dias@qmul.ac.uk |
Public
Adult Critical Care Research
Room 14 Central Tower
The Royal London Hospital
Whitechapel
London
E1 1FR
United Kingdom
Phone | +44 (0)20 3594 0349 |
---|---|
p.dias@qmul.ac.uk |
Public
Office 14 Critical Care Research Office
4th Floor
Royal London Hospital
London
E1 1BB
United Kingdom
Phone | 02035940353 |
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t.shahid@qmul.ac.uk |
Study information
Study design | International open multi-centre randomized controlled trial |
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Primary study design | Interventional |
Secondary study design | Randomised controlled trial |
Study setting(s) | Hospital |
Study type | Treatment |
Participant information sheet | http://optimiseii.org/documents |
Scientific title | Open, multi-centre, randomised controlled trial of cardiac output-guided fluid therapy with low dose inotrope infusion compared to usual care in patients undergoing major elective gastrointestinal surgery |
Study acronym | OPTIMISE II |
Study objectives | The aim of the study is to establish whether the use of minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid, combined with low dose inotrope infusion for patients undergoing major elective surgery involving the gastrointestinal tract will reduce the incidence of postoperative infection within 30 days of randomisation. |
Ethics approval(s) | London - Brent Research Ethics Committee, 28/11/2016, ref: 16/LO/2067 |
Health condition(s) or problem(s) studied | Major elective gastrointestinal surgery |
Intervention | Following provision of informed consent, participants will be randomly allocated to one of two groups (1:1) using a computer generated dynamic procedure (minimisation) with a random component. Minimisation will be performed by country and surgical procedure category. Intervention group: The intervention will commence from the induction of general anaesthesia and continue for four hours following surgery. Cardiac output and stroke volume will be measured by cardiac output monitor. Investigators may only use commercially available cardiac output monitoring equipment provided by Edwards Lifesciences in this trial. No more than 500ml of intra-venous fluid will be administered prior to commencing cardiac output monitoring. In addition to the maintenance fluid and blood products, patients will receive 250ml fluid challenges with a recommended solution as required in order to achieve a maximal value of stroke volume. The absence of fluid responsiveness will be defined as the absence of a sustained rise in stroke volume of at least 10% for 20 minutes or more. In addition, patients will receive a low dose inotrope infusion at a fixed rate which will be commenced after fluid replacement has been initiated. The choice of inotrope will be made at the discretion of the local investigator, according to local preference and availability. The options are dobutamine at a dose/rate of 2.5 µg/kg/min and dopexamine at an equipotent dose/rate of 0.5 µg/kg/min. The infusion rate will be reduced and/or discontinued if the patient develops a tachycardia (heart rate greater than 100bpm) for more than 30 minutes despite adequate anaesthesia and analgesia. Data collection and follow-up for such patients will be performed as normal. All other management decisions will be taken by clinical staff. Control group: Patients in the control group will be managed by clinical staff according to usual practice. This will include 250ml fluid challenges with a recommended intra-venous fluid administered at the discretion of the clinician guided by pulse rate, arterial pressure, urine output, core-peripheral temperature gradient, serum lactate and base excess. If a specific haemodynamic end-point for fluid challenges is to be used, the most appropriate would usually be a sustained rise in central venous pressure of at least 2 mmHg for 20 minutes or more. Patients should not be randomised if the clinician intends to use cardiac output monitoring regardless of study group allocation; this is considered ‘clinician refusal’ and is a specific exclusion criteria. However, clinical staff are free to request cardiac output monitoring if this is required to inform the treatment of a patient who becomes critically ill (e.g. because of severe haemorrhage) during the trial intervention period. In this situation a protocol deviation form will be completed. All participants will be followed for 180 days after randomization. |
Intervention type | Other |
Primary outcome measure | Postoperative infection rate within 30 days of randomisation. This is defined as one or more of the following infections of Clavien-Dindo grade II or greater: 1. Superficial surgical site infection 2. Deep surgical site infection 3. Organ space surgical site infection 4. Pneumonia 5. Urinary tract infection 6. Laboratory confirmed blood stream infection 7. Infection, source uncertain; this is defined as an infection which could be more than one of the above but it is unclear which The primary outcome will be assessed using information from a patient’s medical notes. Patients discharged from hospital before day 30 will be contacted shortly after day 30 to ascertain whether they have received any new treatment since discharge, or if they have been re-admitted to hospital or seen a doctor since discharge. For patients who have received further treatment or seen a health professional since discharge, further details will be collected directly from the hospital/doctor or from the patient’s health records. |
Secondary outcome measures | 1. Mortality, assessed by a patient medical record review or data from national databases, within 180 days of randomisation 2. Acute kidney injury of Clavien-Dindo grade II or greater, assessed using a patient medical note review and telephone interview in the same way as primary outcome, within 30 days from randomisation. 3. Acute cardiac event of Clavien-Dindo grade II or greater, assessed by a review of the patient's medical notes, within 24 hours of randomisation 4. Acute cardiac event of Clavien-Dindo grade II or greater, assessed using a patient medical note review and telephone interview in the same way as primary outcome, within 30 days of randomisation. Process measures: 1. Duration of hospital stay (number of days from randomisation until hospital discharge), assessed by a review of the patient's medical records. 2. Number of critical care free days*, assessed by a review of the patient's medical records, up to 30 days from randomisation. *A critical care free day is defined as a day in which the patient is alive and is not in a level 2 or level 3 critical care bed. |
Overall study start date | 30/08/2016 |
Completion date | 31/03/2023 |
Eligibility
Participant type(s) | Patient |
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Age group | Senior |
Lower age limit | 65 Years |
Sex | Both |
Target number of participants | 2502 (1251 per arm) |
Total final enrolment | 2502 |
Key inclusion criteria | 1. Age 65 years and over 2. Patients undergoing major elective surgery involving the gastrointestinal tract that is expected to take longer than 90 minutes |
Key exclusion criteria | 1. Inability or refusal to provide patient consent 2. Clinician refusal (including intention to monitor cardiac output from the start of surgery regardless of study group allocation) 3. American Society of Anesthesiologists (ASA) score of I 4. Patients expected to die within 30 days 5. Acute myocardial ischaemia within 30 days prior to randomisation 6. Acute pulmonary oedema within 30 days prior to randomisation 7. Contra-indication to low-dose inotropic medication 8. Pregnancy at time of enrolment 9. Previous enrolment in the OPTIMISE II trial 10. Current participation in another clinical trial of a treatment with a similar biological mechanism or primary outcome measure |
Date of first enrolment | 31/12/2016 |
Date of final enrolment | 13/09/2022 |
Locations
Countries of recruitment
- Australia
- Canada
- England
- Germany
- Scotland
- Spain
- Sweden
- United Kingdom
- United States of America
- Wales
Study participating centres
London
E1 1BB
United Kingdom
Taunton
TA1 5DA
United Kingdom
Newport
NP20 2UB
United Kingdom
Old Dalkeith Road
Edinburgh
EH16 4SA
United Kingdom
Fulwood
Preston
PR2 9HT
United Kingdom
Warwick
CV34 5BW
United Kingdom
King's Lynn
PE30 4ET
United Kingdom
Southampton
SO16 6YD
United Kingdom
PO Box 5555
Heidelberg
Victoria
Melbourne
3084
Australia
Fitzroy
Victoria
Melbourne
3065
Australia
Westmead
New South Wales
Sydney
2145
Australia
Toronto
M5G 2C4
Canada
Hamilton
L8N 3Z5
Canada
Marburg
35043
Germany
Bonn
53127
Germany
Berlin
10249
Germany
Berlin
13353
Germany
Hamburg
20246
Germany
Kiel
24105
Germany
Lübeck
23538
Germany
Oldenburg
26129
Germany
Valladolid
47012
Spain
Valladolid
47003
Spain
Madrid
28034
Spain
Madrid
28031
Spain
Madrid
28007
Spain
València
46010
Spain
León
24001
Spain
Santa Cruz de Tenerife
38010
Spain
Lund
222 41
Sweden
Tennessee
Nashville
37232
United States of America
North Carolina
Durham
27710
United States of America
California
Los Angeles
90095
United States of America
New York
New York
11794
United States of America
Texas
Houston
77030
United States of America
Virginia
Charlottesville
22903
United States of America
Sponsor information
University/education
Joint Research Management Office
5 Walden Street
London
E1 2EF
England
United Kingdom
Website | http://bartshealth.nhs.uk/research/about-us/contact-us/ |
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https://ror.org/026zzn846 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
No information available
Results and Publications
Intention to publish date | 31/10/2023 |
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Individual participant data (IPD) Intention to share | Yes |
IPD sharing plan summary | Available on request |
Publication and dissemination plan | Planned publication in a peer reviewed journal, conference presentations and webcasts. Intent to publish the main paper as soon as possible after completion of the trial. |
IPD sharing plan | The datasets generated and analysed during the current study will be available upon request from pctu-data-sharing@qmul.ac.uk. The Pragmatic Clinical Trials Unit (PCTU) shares data via a data-sharing agreement which is submitted to a panel. Enquiries can be sent to the data sharing email address pctu-data-sharing@qmul.ac.uk. Ideally, the Chief Investigator (CI), Professor Rupert Pearse, should be contacted first with the enquiry at admin@optimiseii.org for CI approval. Data would typically only be available to share at the end of the study. Please see the following page for further details regarding PCTU data sharing: https://www.qmul.ac.uk/pctu/collaborate-with-us/data-sharing. |
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
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Protocol article | protocol | 15/01/2019 | 12/02/2020 | Yes | No |
Statistical Analysis Plan | version 3.0 | 17/01/2023 | 24/02/2023 | No | No |
HRA research summary | 28/06/2023 | No | No | ||
Results article | 03/12/2024 | 04/12/2024 | Yes | No |
Additional files
Editorial Notes
04/12/2024: Publication reference added.
18/04/2024: The contact confirmed the record is up to date.
04/07/2023: The following changes were made to the study record:
1. A public contact was replaced and the plain English summary was updated accordingly.
2. The intention to publish date was changed from 30/06/2023 to 31/10/2023.
02/06/2023: The intention to publish date has been changed from 30/06/2023 to 31/08/2023.
24/02/2023: The following changes were made to the trial record:
1. A public contact was removed and a scientific contact updated
2. The recruitment end date was changed from 31/12/2022 to 13/09/2022.
3. The overall trial end date was changed from 31/12/2022 to 31/03/2023 and the plain English summary was updated accordingly.
4. Total final enrolment number added.
5. Statistical analysis plan added.
17/08/2022: The recruitment end date has been changed from 30/06/2022 to 31/12/2022.
25/01/2021: IPD sharing statement added.
16/12/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2020 to 30/06/2022.
2. The overall trial end date was changed from 25/09/2021 to 31/12/2022.
3. The intention to publish date was changed from 25/09/2022 to 30/06/2023.
19/10/2020: Recruitment has resumed.
04/05/2020: Due to current public health guidance, recruitment for this study has been paused.
12/02/2020: Publication reference added.
09/04/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2019 to 31/12/2020.
2. Public contacts were added.
02/04/2019: The condition has been changed from "Topic: Critical Care and Perioperative medicine. Target condition: Patients undergoing major elective gastrointestinal surgery." to "Major elective gastrointestinal surgery" following a request from the NIHR.
11/03/2019: Internal review.