Restrictive vs Liberal Transfusion Strategy on Cardiac Injury in Patients Undergoing Surgery for Fractured Neck Of Femur (RESULT-NOF)

The Impact of Restrictive Versus Liberal Transfusion Strategy on Cardiac Injury in Patients Undergoing Surgery for Fractured Neck Of Femur Study

The investigator wishes to see if it is possible to undertake a study comparing blood transfusion at two different levels of anaemia to see which is best for patients. All patients that present to hospital with a broken hip will be able to take part in the study. If they become anaemic during their treatment they will be allocated to either be transfused when their blood count is less that 9 or less than 7. In all patients, we will measure heart damage with a blood test that is very sensitive. The investigator will also collect data on the incidence of heart attacks and other complications.

Study Overview

• Status: Completed
• Conditions: Anemia; Kidney Injury; Cardiac Event; Fractured Hip
• Intervention / Treatment: Biological: Administration of Red Cell

Detailed Description

Many frail and elderly patients undergo surgery for hip fractures every year. Many of these patients have other health problems including heart disease and anaemia (low haemoglobin or "low blood count") either from chronic illness, from bleeding at the time of their injury or during subsequent surgery. The vast majority (more than 95%) of these patients will go on to have surgery. This surgery is often high risk. Patients with this type of injury may already be frail, may be in hospital for a long time and will need rehabilitation. Many of them will develop complications, including heart attacks and some will die.

Doctors looking after these patients commonly prescribe a blood transfusion around the time of surgery. These patient often have anaemia before surgery an lose more blood during their operations. A benefit of blood transfusion is that it may increase the amount of oxygen the blood can carry. One of the main reasons that doctors prescribe blood around the time of surgery is to prevent heart attacks, which can occur if the heart doesn't receive enough oxygen. Another possible benefit of blood transfusion is that it may help patients get out of bed more quickly after surgery. This is another important aspect of their recovery.

However, blood transfusions can have side effects such as causing heart failure or increasing infections after surgery. These can delay patient recovery too. Although some research has been done in this area, anaesthetists and surgeons are still unsure of when to prescribe blood transfusions to these patients. In particular, uncertainty about how low the blood count should be before a blood transfusion is ordered. Some doctors prescribe blood when the haemoglobin count is less than 9 and some at a lower level of 7. Current guidelines suggest that prescribing at a lower haemoglobin count is better, but there is research which suggests that this level is too low if the patient has a history of heart disease.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom
    • Royal Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:Adults aged over 50 years Within 48 hours of admission to hospital with fractured Neck of Femur. Exclusion Criteria: Age <50

• Refusal of consent of patient (or consultee) Patient for palliative care.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Restrictive; Restrictive transfused when Hb at or below 70	Biological: Administration of Red Cell; Transfusion of red cells dependent on haemoglobin level. Either transfused at haemoglobin of 7 or 9.
Active Comparator: Liberal; Will receive blood transfusion when Hb drops below or equal to 90	Biological: Administration of Red Cell; Transfusion of red cells dependent on haemoglobin level. Either transfused at haemoglobin of 7 or 9.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial Injury	Myocardial injury defined as a high sensitivity cardiac Troponin 1 (Troponin) concentration above the upper reference limit [URL] OF 16 ng L and 34 ng L in women and men respectively at any time during the study period.	Upto 60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial Infarction	Myocardial Infarction defined per the universal definition within 30 days of surgery or before hospital discharge, whichever occurs first.	within 30 days of surgery
Mortality	Mortality (30; 60 days from day of surgery).	upto 60 days following surgery
Diagnosis of Major Adverse Cardiac Events	New diagnosis of MACE within 30 days of surgery or before hospital discharge, whichever occurs first.	within 30 days or before hospital discharge
Acute Kidney Injury	New diagnosis of Acute Kidney Injury	within 30 days of surgery or before discharge from hospital whichever occurs first.
Infections	New diagnosis of Infectious Complications	within 30 days of surgery or before hospital discharge, whichever is first.
Delirium	New diagnosis of Delirium	within 30 days of surgery or before hospital discharge, whichever occurs first.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Troponin	Peak troponin concentration	within 7 days of surgery (ngL )
Troponin -Time	Area under a Troponin-Time curve	within 7 days of surgery
Red cells transfused	Number of units red cells transfused	within7 days of surgery and within 30 days of surgery or before hospital discharge, whichever occurs first.
Volume in mls of Red Cells Transfused.	Volume of red blood cells transfused in mls	within 7 days of surgery and within 30 days of surgery or before hospital discharge, whichever occurs first.
Haemoglobin postoperatively	Postoperative Hb on postoperative days	days 1,3,5,7 after surgery
Nadir Hb	Nadir Hb	within 7 days of surgery and within 30 days of surgery or before hospital discharge, whichever occurs first.
Hospital Admission	Duration of hospital admission (days)	from admission to discharge date from hospital upto 60 days.
Readmission to hospital	Incidence of unplanned hospital readmission within 60 days	upto 60 days of hospital discharge date
Destination	Discharge destination (home, other hospital, nursing home, other)	at Discharge from hospital with fractured hip upto 60 days of admission
Health Related Quality of Life	HRQoL at 60 days (EQ 5D)	at 60 days after surgery
Costs	Secondary care costs during 60 days post-randomisation in Great British Pound	60 days post randomisation

Collaborators and Investigators

• Sponsor: NHS Lothian
• Investigators: Principal Investigator: Dr.Mike Gillies, Associate Medical Director

Publications and helpful links

General Publications

• Carson JL, Stanworth SJ, Dennis JA, Trivella M, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021 Dec 21;12(12):CD002042. doi: 10.1002/14651858.CD002042.pub5.
• Holst LB, Petersen MW, Haase N, Perner A, Wetterslev J. Restrictive versus liberal transfusion strategy for red blood cell transfusion: systematic review of randomised trials with meta-analysis and trial sequential analysis. BMJ. 2015 Mar 24;350:h1354. doi: 10.1136/bmj.h1354.
• Acheson AG, Brookes MJ, Spahn DR. Effects of allogeneic red blood cell transfusions on clinical outcomes in patients undergoing colorectal cancer surgery: a systematic review and meta-analysis. Ann Surg. 2012 Aug;256(2):235-44. doi: 10.1097/SLA.0b013e31825b35d5.
• Fowler AJ, Ahmad T, Phull MK, Allard S, Gillies MA, Pearse RM. Meta-analysis of the association between preoperative anaemia and mortality after surgery. Br J Surg. 2015 Oct;102(11):1314-24. doi: 10.1002/bjs.9861.
• Davenport DL, Bowe EA, Henderson WG, Khuri SF, Mentzer RM Jr. National Surgical Quality Improvement Program (NSQIP) risk factors can be used to validate American Society of Anesthesiologists Physical Status Classification (ASA PS) levels. Ann Surg. 2006 May;243(5):636-41; discussion 641-4. doi: 10.1097/01.sla.0000216508.95556.cc.
• Gillies MA, Ghaffar S, Moppett IK, Docherty AB, Clarke S, Rea N, Stephen J, Keerie C, Ray DC, White TO, MacLullich AMJ, Mills NM, Rowley MR, Murthy K, Pearse RM, Stanworth SJ, Walsh TS. A restrictive versus liberal transfusion strategy to prevent myocardial injury in patients undergoing surgery for fractured neck of femur: a feasibility randomised trial (RESULT-NOF). Br J Anaesth. 2021 Jan;126(1):77-86. doi: 10.1016/j.bja.2020.06.048. Epub 2020 Jul 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: February 22, 2017
• First Submitted That Met QC Criteria: January 16, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): March 11, 2020
• Last Update Submitted That Met QC Criteria: March 9, 2020
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Leg Injuries; Femoral Fractures; Hip Injuries; Hip Fractures; Wounds and Injuries; Fractures, Bone; Femoral Neck Fractures
• Other Study ID Numbers: WKRO-2016-0018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No