Condition category
Surgery
Date applied
15/11/2016
Date assigned
23/11/2016
Last edited
23/11/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

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 September 2021

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)
p.dias@qmul.ac.uk
2. Miss Ann Thomson (public)
ann.thomson@qmul.ac.uk

Trial website

http://optimiseii.org/

Contact information

Type

Scientific

Primary contact

Dr Priyanthi Dias

ORCID ID

Contact details

Adult Critical Care Research
Room 14 Central Tower
The Royal London Hospital
Whitechapel
London
E1 1BB
United Kingdom
+44 20 3594 0352
p.dias@qmul.ac.uk

Type

Public

Additional contact

Miss Ann Thomson

ORCID ID

Contact details

Yvonne Carter Building
58 Turner Street
Whitechapel
London
E1 2AB
United Kingdom
+44 20 7882 2556
ann.thomson@qmul.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

011560

Study information

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

Acronym

OPTIMISE II

Study hypothesis

The aim of the study is to establish whether the use of minimally invasive cardiac output monitoring to guide protocolised administration of intra-venous 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

London - Brent Research Ethics Committee, 28/11/2016, ref: 16/LO/2067

Study design

International open multi-centre randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

http://optimiseii.org/documents

Condition

Topic: Critical Care and Perioperative medicine.
Target condition: Patients undergoing 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

Phase

Drug names

Primary outcome measures

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 trial start date

30/08/2016

Overall trial end date

25/09/2021

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

2502 (1251 per arm)

Participant 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

Recruitment start date

31/12/2016

Recruitment end date

31/12/2019

Locations

Countries of recruitment

Australia, Canada, Germany, Spain, Sweden, United Kingdom, United States of America

Trial participating centre

Royal London Hospital
Whitechapel Road
London
E1 1BB
United Kingdom

Trial participating centre

Musgrove Park Hospital
Parkfield Drive
Taunton
TA1 5DA
United Kingdom

Trial participating centre

Royal Gwent Hospital
Cardiff Road
Newport
NP20 2UB
United Kingdom

Trial participating centre

Royal Infirmary of Edinburgh
51 Little France Crescent Old Dalkeith Road
Edinburgh
EH16 4SA
United Kingdom

Trial participating centre

Royal Preston Hospital
Sharoe Green Lane North Fulwood
Preston
PR2 9HT
United Kingdom

Trial participating centre

Warwick Hospital
Lakin Road
Warwick
CV34 5BW
United Kingdom

Trial participating centre

The Queen Elizabeth Hospital King's Lynn
Gayton Road
King's Lynn
PE30 4ET
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Austin Hospital
145 Studley Road PO Box 5555 Heidelberg Victoria
Melbourne
3084
Australia

Trial participating centre

St Vincent’s Hospital Melbourne
41 Victoria Parade Fitzroy Victoria
Melbourne
3065
Australia

Trial participating centre

Westmead Hospital
Cnr Hawkesbury Road and Darcy Road Westmead New South Wales
Sydney
2145
Australia

Trial participating centre

Toronto General Hospital
200 Elizabeth Street
Toronto
M5G 2C4
Canada

Trial participating centre

McMaster Hospital
1200 Main St. West
Hamilton
L8N 3Z5
Canada

Trial participating centre

University Hospital Giessen
Baldingerstraße
Marburg
35043
Germany

Trial participating centre

University Hospital Bonn
Sigmund-Freud-Straße 25
Bonn
53127
Germany

Trial participating centre

Vivantes Hospital Berlin-Friedrichshain
Landsberger Allee 49
Berlin
10249
Germany

Trial participating centre

Charité Berlin Campus Virchow and Mitte
Augustenburger Pl. 1
Berlin
13353
Germany

Trial participating centre

UKE Hamburg
Martinistraße 52
Hamburg
20246
Germany

Trial participating centre

University Hospital Schleswig-Holstein Kiel
Campus Kiel, Schwanenweg 21
Kiel
24105
Germany

Trial participating centre

University Hospital Lübeck
Ratzeburger Allee 160
Lübeck
23538
Germany

Trial participating centre

University Hospital Oldenburg
Ammerländer Heerstr. 114-118
Oldenburg
26129
Germany

Trial participating centre

Hospital Universitario Rio Hortega Valladolid
Calle Dulzaina, 2
Valladolid
47012
Spain

Trial participating centre

Hospital Clínico Universitario Valladolid
Av. Ramón y Cajal, 3
Valladolid
47003
Spain

Trial participating centre

Hospital Ramon y Cajal de Madrid
Ctra. Colmenar Viejo, km. 9,100
Madrid
28034
Spain

Trial participating centre

Hospital Universitario Infanta Leonor Madrid
Av Gran Via del Este, 80
Madrid
28031
Spain

Trial participating centre

Hospital Gregorio Marañon Madrid
Calle del Dr. Esquerdo, 46
Madrid
28007
Spain

Trial participating centre

Hospital Clinico Universitario Valencia
nº, Av. de Blasco Ibáñez, 17
València
46010
Spain

Trial participating centre

Complejo Hospitalario de León
Altos de Navas, s/n
León
24001
Spain

Trial participating centre

Hospital Universitario Nuestra Señora de la Candelaria Tenerifa
Ctra. del Rosario, 145
Santa Cruz de Tenerife
38010
Spain

Trial participating centre

University Hospital Lund
Getingevägen 4
Lund
222 41
Sweden

Trial participating centre

Vanderbilt University Medical Centre
1211 Medical Center Drive Tennessee
Nashville
37232
United States of America

Trial participating centre

Duke University Hospital
2301 Erwin Road North Carolina
Durham
27710
United States of America

Trial participating centre

Ronald Reagan UCLA Medical Centre
757 Westwood Plaza California
Los Angeles
90095
United States of America

Trial participating centre

Stony Brook University Hospital
101 Nicolls Rd New York
New York
11794
United States of America

Trial participating centre

The University of Texas MD Anderson Cancer Centre
1515 Holcombe Blvd Texas
Houston
77030
United States of America

Trial participating centre

University of Virginia Health System
1215 Lee St Virginia
Charlottesville
22903
United States of America

Sponsor information

Organisation

Queen Mary University of London

Sponsor details

Joint Research Management Office
5 Walden Street
London
E1 2EF
United Kingdom

Sponsor type

University/education

Website

http://bartshealth.nhs.uk/research/about-us/contact-us/

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Funder name

Edwards Lifesciences Corporation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

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 current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

25/09/2022

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes