FUNNY
Research type
Research Study
Full title
Targeted heart rate control using the funny current inhibitor ivabradine to reduce morbidity in patients undergoing non-cardiac surgery: a phase IIa, triple blind, placebo controlled randomised trial
IRAS ID
1003561
Contact name
Gareth Ackland
Contact email
Sponsor organisation
Joint Research Office
Eudract number
2020-002099-11
ISRCTN Number
ISRCTN12903789
Research summary
The development of serious medical problems after surgery (e.g. damage to the heart) can adversely affect the patient's care particularly in the
older more vulnerable population. A poor postoperative outcome not only delays patient recovery but poses longer-term health concerns such as
loss of mobility and independence. There is a clear and urgent need to improve perioperative care to effectively improve patient outcomes.
We know patients who are most vulnerable to developing complications often have problems with a specialised nerve that helps control their heart
beat. A key feature in these patients is a higher heart beat, which is strongly associated with heart damage and coincides with other organs of the
body not working normally. However current treatments that slow heart rate (e.g. beta-blockers) can result in further damage being done because
of indirect effects caused by
these drugs on blood pressure and other functions.
Our aim is to establish whether the specific lowering of a patient’s heart rate during their perioperative care (the care before, during and after
surgery) will protect them from damage to the heart and reduce the development of further complications. In this trial, the drug ivabradine will be
used which slows heart rate only. We will invite 350 patients having surgery that does not involve to take part. We will randomly allocate them (like
a coin toss) to receive ivabradine tablets or placebo tablets for a maximum of three days from the day of surgery. After surgery, researchers who
don't know which patients have been given ivabradine will measure their safety and well being.Lay summary of study results:
People having major surgery that does not involve the heart can sometimes develop injury to the heart around the time of their operation. This may occur without obvious symptoms but can be associated with complications and poorer recovery. A faster heart rate has been linked with a greater risk of this type of heart injury. However, it is not known whether actively lowering the heart rate can reduce this risk.
This study investigated whether a medicine called ivabradine could reduce heart injury and complications following non-heart surgery. Ivabradine lowers the heart rate without having some of the other effects on the heart and blood pressure associated with commonly used heart-rate-lowering medicines.
The study included 350 people aged 55 years or older who were considered to be at increased risk of heart injury and were undergoing planned non-heart surgery at several hospitals. Participants were randomly allocated to receive either ivabradine or an inactive treatment (placebo). Neither the participants nor the clinical and research teams knew which treatment an individual participant received during the study.
Treatment was started before surgery. The dose of ivabradine was adjusted according to each participant's heart rate and could be given for up to 48 hours. The researchers assessed whether participants developed heart injury within 72 hours of surgery together with complications occurring within seven days.
Follow-up information was available for 343 participants. Heart injury with associated complications occurred in 34.3% of participants allocated to ivabradine and 32.2% of those allocated to placebo. There was no evidence that ivabradine reduced the risk of these outcomes.
Ivabradine did successfully lower participants' heart rates compared with placebo, showing that the treatment achieved the intended biological effect. However, this reduction in heart rate did not result in fewer heart injuries or associated complications. The findings were similar when the results were analysed in several different ways.
Across participants, lower overall heart rates around the time of surgery were associated with fewer complications. However, because actively lowering heart rate with ivabradine did not improve outcomes, the study suggests that simply targeting heart rate using this medicine is unlikely to prevent heart injury or related complications following non-heart surgery.
These findings improve our understanding of the relationship between heart rate and complications following surgery and may help guide the design of future treatments and research aimed at reducing heart-related complications after major surgery.REC name
London - Westminster Research Ethics Committee
REC reference
21/LO/0069
Date of REC Opinion
4 Jun 2021
REC opinion
Further Information Favourable Opinion