Condition category
Circulatory System
Date applied
10/04/2017
Date assigned
11/04/2017
Last edited
20/02/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
The best blood pressure target to guide treatment in critical care is not known. It is, however, well-known that both very low blood pressure (severe hypotension) and, side effects from medications that increase blood pressure (vasopressors), can increase the risk of death. Current guidelines recommend that clinicians aim for a mean arterial pressure (MAP) of 65 mmHg or more. These guidelines are based on low quality evidence and no guidance is given on an upper limit. Previous research shows MAP values in critical care frequently rise significantly higher than 65 mmHg, exposing patients to potentially unnecessary doses of vasopressors and associated side-effects. There is emerging evidence suggesting that using a lower MAP target (permissive hypotension) to guide treatment may increase survival in older critically ill patients. A large clinical trial is therefore needed to evaluate this idea. The aim of this study is to evaluate the clinical and cost-effectiveness of permissive hypotension (MAP target of 60 - 65 mmHg during vasopressor therapy) in critically ill patients aged 65 years or over with hypotension.

Who can participate?
Older adults with low blood pressure who are to be treated with blood pressure raising medication.

What does the study involve?
Eligible participants are randomly allocated to one of two groups. Participants in the first group are treated using the 60 – 65 mmHg MAP target when they need vasopressor therapy in the in the critical care unit. Participants in the second group continue to receive usual care (as per local practices). Participants are approached to provide consent to take part once they are well enough to do so. Participants are then sent questionnaires about their wellbeing and quality of life to complete at 90 days and one year (only patients recruited during the first nine months of the recruitment period are contacted at one year). In addition, survival rates and information about lengths of hospital stays are recorded using patient notes.

What are the possible benefits and risks of participating?
The benefits and risks of using a lower blood pressure target to guide treatment, instead of usual care, are unclear at this time, which is why this research is needed. It is not yet known whether participants will benefit directly from their participating in the 65 Trial. If the permissive hypotension strategy is found to be clinically and cost-effective, then participants in this group may benefit directly in terms of improved survival or by experiencing less side-effects associated with vasopressors. There are no potential significant benefits of taking part for participants in the usual care group, other than the understanding that information from the trial will be used to improve the care of future critically ill patients. There are no notable risks associated with this study.

Where is the study run from?
65 adult, general, critical care units at NHS hospitals in England, Northern Ireland and Wales (UK)

When is the study starting and how long is it expected to run for?
March 2017 to October 2019

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Mr Alvin Richards-Belle
alvin.richards-belle@icnarc.org

Trial website

https://www.icnarc.org/Our-Research/Studies/Sixty-Five

Contact information

Type

Public

Primary contact

Mr Alvin Richards-Belle

ORCID ID

Contact details

Intensive Care National Audit & Research Centre
Napier House
24 High Holborn
London
WC1V 6AZ
United Kingdom
+44 (0)20 7831 6878
alvin.richards-belle@icnarc.org

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

34223

Study information

Scientific title

Evaluating the clinical and cost-effectiveness of permissive hypotension in critically ill patients aged 65 years or over with vasodilatory hypotension

Acronym

Study hypothesis

The aim of this study is to evaluate the clinical and cost-effectiveness of permissive hypotension (MAP target of 60 - 65 mmHg during vasopressor therapy) in critically ill patients aged 65 years or over with hypotension.

Ethics approval

Oxford C Research Ethics Committee, 24/04/2017, ref: 17/SC/0142

Study design

Randomised; Interventional; Design type: Treatment, Process of Care, Management of Care

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Critical care, Primary sub-specialty: Critical Care; UKCRC code/ Disease: Cardiovascular/ Other and unspecified disorders of the circulatory system

Intervention

Patients will be randomised following a 1:1 sequence to either the intervention group (permissive hypotension) or usual care.

Permissive hypotension group: Patients will be treated using a MAP target range 60 - 65 mmHg whilst receiving vasopressor therapy. The decision to discontinue vasopressors will depend on the patients' ability to maintain the MAP target stipulated by the protocol without vasopressors. The trial treatment will apply at any point the patient requires vasopressors during their admission in the critical care unit.

Usual care group: Patients will continue to receive usual care (as per local practices).

Follow-up for survival status at 90 days and at one year will also be obtained via data-linkage with nationally held records. At each time-point, survivors will be posted a questionnaire containing the EQ-5D-5L, IQCODE (short version) and health services questionnaire. Only patients recruited during the first nine months of the recruitment period will be contacted at one year.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Clinical evaluation:
All-cause mortality is assessed through data-linkage with nationally held death registrations at 90 days.

Economic evaluation:
Incremental net monetary benefit (INB), evaluated at the NICE recommended threshold of £20,000 per quality-adjusted life year (QALY), at 90 days.

Secondary outcome measures

1. Mortality at discharge from the critical care unit and acute hospital is assessed by reviewing patient medical notes at critical care unit discharge
2. Duration of survival is assessed through data-linkage with nationally held death registrations at the longest available follow-up (e.g. patients will be followed up for a minimum of six months following randomisation, with the earliest recruited patients followed-up for survival to 24 months)
3. Duration of advanced respiratory and renal support (defined according to the Critical Care Minimum Dataset [CCMDS]) during the critical care unit stay is assessed by reviewing patient medical notes at critical care unit discharge
4. Days alive and free of advanced respiratory support and renal support is assessed by reviewing patient medical notes at critical care unit discharge
5. Duration of critical care unit and acute hospital stay is assessed by reviewing patient medical notes at critical care unit and hospital discharge
6. Cognitive function is assessed using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE, short version) at 90 days and one year
7. Health-related quality of life is assessed using the EuroQol EQ-5D-5L questionnaire at 90 days and one year
8. Resource use and costs is assessed using a health services questionnaire at 90 days and one year
9. Estimated lifetime incremental cost-effectiveness

Overall trial start date

01/03/2017

Overall trial end date

31/10/2019

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 16/02/2018:
1. Age 65 years or older
2. Vasodilatory hypotension as assessed by treating clinician
3. Started infusion (for at least one hour) of vasopressors within prior 6 hours (if noradrenaline, then a minimum dose of 0.1 μg kg-1 min-1)
4. Adequate fluid resuscitation is completed or ongoing
5. Vasopressors expected to continue for 6 hours or more as assessed by treating clinician

Previous inclusion criteria:
1. Age 65 years or older
2. Vasodilatory hypotension as assessed by treating clinician
3. Decision to start vasopressors or started within prior 6 hours following/during adequate fluid resuscitation
4. Vasopressors expected to continue for 6 hours or more as assessed by treating clinician

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 1440; UK Sample Size: 1440

Participant exclusion criteria

1. Vasopressors being used solely as therapy for bleeding, acute ventricular failure (left or right) or post-cardiopulmonary bypass vasoplegia
2. Ongoing treatment for brain injury or spinal cord injury
3. Death perceived as imminent
4. Previous enrolment to the 65 Trial

Recruitment start date

03/07/2017

Recruitment end date

28/02/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Poole Hospital
Longfleet Road
Poole
BH15 2JB
United Kingdom

Trial participating centre

Darent Valley Hospital
Darenth Wood Road
Dartford
DA2 8DA
United Kingdom

Trial participating centre

Medway Maritime Hospital
Windmill Road
Gillingham
ME7 5NY
United Kingdom

Trial participating centre

Bristol Royal Infirmary
Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom

Trial participating centre

Royal Berkshire Hospital
Craven Road
Reading
RG1 5AN
United Kingdom

Sponsor information

Organisation

Intensive Care National Audit & Research Centre

Sponsor details

Napier House
24 High Holborn
London
WC1V 6AZ
United Kingdom
+44 (0)20 7269 9277
icnarc@icnarc.org

Sponsor type

Hospital/treatment centre

Website

www.icnarc.org

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

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

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

31/10/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

20/02/2018: Internal review. 16/02/2018: Inclusion criteria updated. 30/05/2017: The date of ethical approval has been added.