| ISRCTN | ISRCTN10580502 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10580502 |
| Secondary identifying numbers | CPMS 34223 |
- Submission date
- 10/04/2017
- Registration date
- 11/04/2017
- Last edited
- 03/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
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 14 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
Contact information
Public
Intensive Care National Audit & Research Centre
Napier House
24 High Holborn
London
WC1V 6AZ
United Kingdom
| Phone | +44 (0)20 7831 6878 |
|---|---|
| alvin.richards-belle@icnarc.org |
Study information
| Study design | Randomized; Interventional; Design type: Treatment, Process of Care, Management of Care |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Evaluating the clinical and cost-effectiveness of permissive hypotension in critically ill patients aged 65 years or over with vasodilatory hypotension |
| 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(s) | Oxford C Research Ethics Committee, 24/04/2017, ref: 17/SC/0142 |
| Condition | Hypotension |
| Intervention | Current intervention as of 20/03/2019: 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 14 months of the recruitment period will be contacted at one year. Previous 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 |
| Primary outcome measure | 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 study start date | 01/03/2017 |
| Overall study end date | 31/10/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Senior |
| Lower age limit | 65 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 2600; UK Sample Size: 2600 |
| Total final enrolment | 2600 |
| 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 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 | 16/03/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Poole
BH15 2JB
United Kingdom
Dartford
DA2 8DA
United Kingdom
Gillingham
ME7 5NY
United Kingdom
Bristol
BS2 8HW
United Kingdom
Reading
RG1 5AN
United Kingdom
Sponsor information
Hospital/treatment centre
Napier House
24 High Holborn
London
WC1V 6AZ
England
United Kingdom
| Phone | +44 (0)20 7269 9277 |
|---|---|
| icnarc@icnarc.org | |
| Website | www.icnarc.org |
"ROR" |
https://ror.org/057b2ek35 |
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
Results and Publications
| Intention to publish date | 31/10/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 09/09/2019 | 13/09/2019 | Yes | No | |
| Statistical Analysis Plan | statistical and health economic analysis plan | 03/07/2019 | 13/09/2019 | Yes | No |
| Results article | 12/02/2020 | 13/02/2020 | Yes | No | |
| Results article | 01/02/2021 | 03/03/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol article | 08/12/2020 | 03/05/2024 | Yes | No |
Editorial Notes
03/05/2024: Publication reference added.
01/07/2022: Internal review.
03/03/2021: Publication reference added.
13/02/2020: Publication reference added.
13/09/2019: Publication references added.
28/03/2019: Internal review.
26/03/2019: The following changes were made:
1. The recruitment end date was changed from 31/03/2019 to 16/03/2019.
2. The total final enrolment was added.
3. The condition has been changed from "Specialty: Critical care, Primary sub-specialty: Critical Care; UKCRC code/ Disease: Cardiovascular/ Other and unspecified disorders of the circulatory system" to "" following a request from the NIHR.
20/03/2019: The following changes have been made:
1. The recruitment end date has been changed from 28/02/2019 to 31/03/2019.
2. The intervention was updated.
3. The plain English summary has been changed to reflect the change to the intervention.
09/07/2018: The target number of participants was changed from 1440 to 2600.
20/02/2018: Internal review.
16/02/2018: Inclusion criteria updated.
30/05/2017: The date of ethical approval has been added.
