Optimisation of perioperative cardiovascular management to improve surgical outcome II

ISRCTN ISRCTN39653756
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
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

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

Study website

Contact information

Dr Priyanthi Dias
Scientific

Adult Critical Care Research
Room 14 Central Tower
The Royal London Hospital
Whitechapel
London
E1 1FR
United Kingdom

ORCiD logoORCID ID 0000-0003-1740-6165
Phone +44 (0)20 3594 0349
Email p.dias@qmul.ac.uk
Dr Priyanthi Dias
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
Email p.dias@qmul.ac.uk
Miss Tasnin Shahid
Public

Office 14 Critical Care Research Office
4th Floor
Royal London Hospital
London
E1 1BB
United Kingdom

Phone 02035940353
Email t.shahid@qmul.ac.uk

Study information

Study designInternational open multi-centre randomized controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet http://optimiseii.org/documents
Scientific titleOpen, 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 acronymOPTIMISE II
Study objectivesThe 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) studiedMajor elective gastrointestinal surgery
InterventionFollowing 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 typeOther
Primary outcome measurePostoperative 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 measures1. 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 date30/08/2016
Completion date31/03/2023

Eligibility

Participant type(s)Patient
Age groupSenior
Lower age limit65 Years
SexBoth
Target number of participants2502 (1251 per arm)
Total final enrolment2502
Key inclusion criteria1. 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 criteria1. 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 enrolment31/12/2016
Date of final enrolment13/09/2022

Locations

Countries of recruitment

  • Australia
  • Canada
  • England
  • Germany
  • Scotland
  • Spain
  • Sweden
  • United Kingdom
  • United States of America
  • Wales

Study participating centres

Royal London Hospital
Whitechapel Road
London
E1 1BB
United Kingdom
Musgrove Park Hospital
Parkfield Drive
Taunton
TA1 5DA
United Kingdom
Royal Gwent Hospital
Cardiff Road
Newport
NP20 2UB
United Kingdom
Royal Infirmary of Edinburgh
51 Little France Crescent
Old Dalkeith Road
Edinburgh
EH16 4SA
United Kingdom
Royal Preston Hospital
Sharoe Green Lane North
Fulwood
Preston
PR2 9HT
United Kingdom
Warwick Hospital
Lakin Road
Warwick
CV34 5BW
United Kingdom
The Queen Elizabeth Hospital King's Lynn
Gayton Road
King's Lynn
PE30 4ET
United Kingdom
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
Austin Hospital
145 Studley Road
PO Box 5555
Heidelberg
Victoria
Melbourne
3084
Australia
St Vincent’s Hospital Melbourne
41 Victoria Parade
Fitzroy
Victoria
Melbourne
3065
Australia
Westmead Hospital
Cnr Hawkesbury Road and Darcy Road
Westmead
New South Wales
Sydney
2145
Australia
Toronto General Hospital
200 Elizabeth Street
Toronto
M5G 2C4
Canada
McMaster Hospital
1200 Main St. West
Hamilton
L8N 3Z5
Canada
University Hospital Giessen
Baldingerstraße
Marburg
35043
Germany
University Hospital Bonn
Sigmund-Freud-Straße 25
Bonn
53127
Germany
Vivantes Hospital Berlin-Friedrichshain
Landsberger Allee 49
Berlin
10249
Germany
Charité Berlin Campus Virchow and Mitte
Augustenburger Pl. 1
Berlin
13353
Germany
UKE Hamburg
Martinistraße 52
Hamburg
20246
Germany
University Hospital Schleswig-Holstein Kiel
Campus Kiel, Schwanenweg 21
Kiel
24105
Germany
University Hospital Lübeck
Ratzeburger Allee 160
Lübeck
23538
Germany
University Hospital Oldenburg
Ammerländer Heerstr. 114-118
Oldenburg
26129
Germany
Hospital Universitario Rio Hortega Valladolid
Calle Dulzaina, 2
Valladolid
47012
Spain
Hospital Clínico Universitario Valladolid
Av. Ramón y Cajal, 3
Valladolid
47003
Spain
Hospital Ramon y Cajal de Madrid
Ctra. Colmenar Viejo, km. 9,100
Madrid
28034
Spain
Hospital Universitario Infanta Leonor Madrid
Av Gran Via del Este, 80
Madrid
28031
Spain
Hospital Gregorio Marañon Madrid
Calle del Dr. Esquerdo, 46
Madrid
28007
Spain
Hospital Clinico Universitario Valencia
nº, Av. de Blasco Ibáñez, 17
València
46010
Spain
Complejo Hospitalario de León
Altos de Navas, s/n
León
24001
Spain
Hospital Universitario Nuestra Señora de la Candelaria Tenerifa
Ctra. del Rosario, 145
Santa Cruz de Tenerife
38010
Spain
University Hospital Lund
Getingevägen 4
Lund
222 41
Sweden
Vanderbilt University Medical Centre
1211 Medical Center Drive
Tennessee
Nashville
37232
United States of America
Duke University Hospital
2301 Erwin Road
North Carolina
Durham
27710
United States of America
Ronald Reagan UCLA Medical Centre
757 Westwood Plaza
California
Los Angeles
90095
United States of America
Stony Brook University Hospital
101 Nicolls Rd
New York
New York
11794
United States of America
The University of Texas MD Anderson Cancer Centre
1515 Holcombe Blvd
Texas
Houston
77030
United States of America
University of Virginia Health System
1215 Lee St
Virginia
Charlottesville
22903
United States of America

Sponsor information

Queen Mary University of London
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/
ROR logo "ROR" https://ror.org/026zzn846

Funders

Funder type

Government

National Institute for Health Research
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
Edwards Lifesciences Corporation

No information available

Results and Publications

Intention to publish date31/10/2023
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planPlanned 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 planThe 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?
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

ISRCTN39653756_SAP_v3.0_17Jan2023.pdf

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.