Comprehensive ascertainment of bleeding in patients prescribed different combinations of dual antiplatelet therapy (DAPT) and triple therapy (TT, DAPT plus an anticoagulant) after coronary interventions in the UK: a population based cohort study

Funder: NIHR/HTA (project number 14/192/89)

Sponsor: University Hospitals Bristol

Status: Set Up

Antiplatelet drugs are used to prevent heart disease and stroke. They work by preventing the formation of blood clots in arteries.

In people who have had a heart attack or have diseased arteries, low-dose aspirin (75 mg daily) is recommended to prevent another heart attack or a stroke. People who have had a coronary stent or coronary artery bypass grafting (CABG) surgery following a heart attack are prescribed low-dose aspirin and an additional antiplatelet drug, for up to 12 months following the event. This is called dual antiplatelet therapy (DAPT). Furthermore, some patients (e.g. those with atrial fibrillation) are also prescribed an anticoagulant (e.g. warfarin, dabigatran, rivaroxaban, or apixaban) in addition to DAPT, which is known as ‘Triple Therapy’.

Antiplatelet therapies increase the risk of bleeding, from minor bruising to more severe symptoms such as gastrointestinal bleeding. Few studies have assessed how often bleeding events happen in people taking DAPT. Hospital doctors are increasingly prescribing more antiplatelet therapy to people who have had a stent or CABG surgery, without taking into account the risk of minor bleeding. The extent of minor bleeding and the effect that it has on patients is not known because most minor bleeding events are treated by GPs and patients do not go to hospital.

The ADAPTT study will use a large GP database of routinely collected data, and a database of patients’ attendances and admissions to hospital, to determine how many people experience bleeding after being prescribed DAPT or DAPT and an anticoagulant. We will compare patients who take aspirin only with patients taking different combinations of DAPT (with or without an anticoagulant).

We will do this for different patient groups (treated with stent, CABG surgery or medication only) and will look into the cost-effectiveness of DAPT. We will also review the literature to determine how bleeding affects quality of life in these individuals. Information from the ADAPTT study will help doctors to choose drugs that are more appropriate for individual patients’ specific needs, which will reduce the risk of bleeding and increase adherence to treatment.

 

Contact Information

Chief Investigator: Dr Maria Pufulete, Research Fellow

Study coordinator: Lucy Dabner

E-mail:  adaptt-study@bristol.ac.uk

 

Association of non-coding RNAs with Coronary Artery Disease and type 2 Diabetes

Status: Set Up

Sponsor: University Hospitals Bristol 

REC Number: 13/LO/1687

Genes hold the information to build and maintain the human body.  They contain the code to produce proteins which perform many functions within our body.  However, genes do not do this alone and instead rely on the help of other molecules.  Recently, scientists have discovered the existence of chemicals called “non-coding” ribonucleic acids (ncRNAs).  These chemicals may influence the production of proteins and have an important role in the heart; some of them can aggravate heart conditions while others can have positive effects. The levels of these chemicals, which are present in the tissues and fluid of the body, may be possible indicators of disease or of the effects of heart surgery.

In Arcadia we are asking participants who undergo cardiac surgery to provide heart biopsies and blood and urine samples, and allow us to use tissue samples left over from surgery.  We are measuring and identifying all non-coding RNAs in these tissues and determining whether their levels are affected by heart disease and diabetes. The study also aims to find out whether we can measure the ncRNAs in blood, urine and tissue of patients undergoing heart surgery, to predict which patients will develop complications.  This study is important because it could help identify treatments to improve the recovery of the patients after heart surgery.

Contact Information

Chief Investigator: Prof. Gianni Angelini

Study coordinatorRachael Heys (Bristol Royal Infirmary), Alima Rahman (Hammersmith Hospital)

E-mailarcadia-study@bristol.ac.uk

 

Ultradian rhythms of cortisol after cardiac surgery

Sponsor: University of Bristol

REC Number: 11/H0107/9

Status: Closed to recruitment

Heart surgery provokes a large stress response in the body, which can lead to complications after surgery.  Cortisol is the main hormone responsible for the stress response, but currently researchers do not know how heart surgery affects cortisol production and whether steroids can be given in a more tailored way. 

The Cortisol study is examining whether heart surgery disrupts the diurnal rhythm of cortisol production, which normally causes cortisol to increase early in the morning and dip by late afternoon.  This rhythm is produced by discreet pulses and researchers believe that disrupting these pulses increases the stress response after surgery. 

We are recruiting men undergoing a coronary artery bypass grafting (CABG) operation to investigate cortisol pulses after surgery.  Women are not being recruited due to the cyclical effects of female hormones on these rhythms. We are also investigating whether the use of the bypass machine during heart surgery influences cortisol production. For this initial part of the study, we allocated a group of similar patients by chance to receive surgery with a bypass machine or surgery without a bypass machine.  

Contact Information

Chief Investigator: Dr Ben Gibbison

Study coordinator: Jon Evans

E-mail: Cortisol-trial@bristol.ac.uk

 

Cortisol profiles in the critically ill after cardiac surgery

Sponsor: Bristol University 

REC Number: 12/SW/0186

Some patients do not recover well from cardiac surgery and become critically ill on life support machines.  One of the causes of this is an uncontrolled inflammatory response. The inflammatory response is what causes your sprained ankle or cut hand to become red and swollen. It gets red because the blood vessels get bigger and it gets swollen because fluid leaks out of the blood vessels and into the tissues. This is helpful if it is a small area, but when it is across the whole body, such as after cardiac surgery it can be problematic and potentially life-threatening.

We all produce a hormone called cortisol (a steroid) that helps protect against an uncontrolled inflammatory response. It is thought that there are some people who do not produce enough cortisol or do not produce it in the right pattern. Doctors often give synthetic cortisol type drugs (corticosteroids) to patients when they are critically ill to reduce this inflammatory response. However, if they are used in too large a dose, these drugs can have significant side effects such as immunosuppression, poor wound healing and a diabetic state. Cortisol is released in discreet pulses throughout the day, called an ultradian rhythm. 

The Cortisol 2 study is investigating what happens to these pulses of cortisol in people who are critically ill.  We are recruiting patients who have had cardiac surgery and go to the cardiac intensive care unit (CICU).  We are taking blood samples over 24 hours to measure cortisol and describe its ultradian rhythm.  Once we know what is ‘normal’ during critical illness, we can begin to design tests to see which patients might benefit from steroids and if so, give them in a more tailored way.

further details >

Contact Information

Chief Investigator: Prof Stafford Lightman

Study coordinator: Jon Evans

E-mail:  cortisol-trial@bristol.ac.uk

 

Summary

Effect of Remote Ischaemic preConditioning on clinical outcomes in patients undergoing Coronary Artery Bypass Graft surgery (ERICCA): A multicentre randomised controlled clinical trial

Cardiac surgery can lead to complications, for example kidney injury and stroke, caused by ischaemia-reperfusion injury. This type of damage to the heart happens when blood flow is restored to the heart after a period of ischaemia, or lack of oxygen.  A strategy that may protect the heart from ischemia-reperfusion injury is remote ischemic preconditioning (RIPC).  RIPC involves inducing ischaemia in the arm or leg, achieved by several cycles of inflating and deflating an arm blood-pressure cuff, just before surgery. 

The Ericca study is allocating patients undergoing cardiac surgery across 30 UK centres by chance to receive either RIPC or a “sham” procedure, in which the blood pressure cuff appears to inflate but there is no actual pressure on the arm.  In this way, neither doctors nor patients will know which treatment was administered.  This is known as a double-blind study. 

We are following patients up for one year to determine whether RIPC reduces the rate of complications, including death, heart attack, stroke, further surgical procedures, after surgery.

further details >

Contact Information

Chief Investigator: Dr Derek J Hausenloy

Trial Co-Ordinator: Wendy Underwood

E-mail:  ericca-trial@bristol.ac.uk

 

Summary

A Singleblinded, Randomized, Controlled, Comparative Phase III Study Evaluating the Safety and Effectiveness of EVARREST™ Fibrin Sealant Patch as an Adjunct to Hemostasis During Cardiovascular Surgery

Bleeding is a major complication during cardiovascular surgery. Various approaches have been developed to control bleeding, including the use of fibrin sealants, which are a type of tissue adhesive that can be applied at the site of bleeding to reduce blood loss and promote wound healing.

The Evarrest study is evaluating the safety and effectiveness of the Evarrest Fibrin Sealant Patch. We are recruiting patients undergoing open surgery on the aorta who experience bleeding.  Patients are allocated by chance to receive either the Evarrest patch or the Tachosil patch, which is currently approved for use during cardiac surgery. 

We will determine whether the Evarrest patch is better than the Tachosil patch at stopping bleeding, and whether it is safe.

further details >

Contact Information

Chief Investigator:

Trial Co-Ordinator: Wendy Underwood/Emma Hopkins

E-mail: evarrest-trial@bristol.ac.uk

 

A randomised controlled trial to assess the axtent of intimal Hyperplasia and Atherogenesis in bypass Vein grafts following different Surgical preparation Techniques

Sponsor: University Hospitals Bristol 

REC Number: 09/H0101/28

Status: Analysis

During coronary artery bypass grafting (CABG) surgery, vein grafts removed from other parts of the body are used to bypass diseased arteries in the heart and improve blood flow.  Vein grafts can become narrow over time and which increases the risk of having another heart attack.

Harvest is designed to test whether the method of surgical preparation of the vein grafts at the time of the operation decreases the risk of blockage one year after surgery.  Currently, vein grafts are prepared by stripping away the surrounding fat at the time the vein is removed from the leg.  The vein is then tested for leaks by filling the graft with fluid under high pressure, using a syringe.  It is thought that this method may damage the vein.  Other methods of preparation involve removing the vein from the leg with its surrounding fat and testing for leaks at lower pressure. 

Patients who consent to take part in Harvest are allocated by chance to different vein harvesting and vein preparation strategies and followed up for one year, when they will have detailed investigations of the vein grafts. 

A total of 97 patients have been successfully randomised over 3 years and 10 months and followed-up for 1 year. The trial is currently in analysis phase and results are expected to be published in summer 2017. 

Contact Information

Chief Investigator: Prof Gianni Angelini

E-mail: harvest-trial@bristol.ac.uk

 

The effectiveness on post-operative recovery of using ‘off pump’ self-expanding tissue valves (IPVR) versus ‘on pump’ conventional tissue valves (PVR) for pulmonary valve replacement: an early phase randomised controlled trial (RCT)

In(jectable) V(alve) I(mplantation) T(rial) (InVITe)

funder: NIHR, Bristol Cardiovascular Biomedical Research Centre (Cardiovascular Theme), and the British Heart Foundation 

Sponsor: University Hospitals Bristol 

REC Number: 15/SW/0179

Many patients who are born with problems with their heart valves require repeated operations throughout their life to replace the affected valves. The standard operation for valve replacement involves opening the chest, extensive exposure by the surgeon and the use of the heart-lung bypass machine to take over the function of the heart and lungs (pumping blood and oxygen through the body) during the operation. The heart-lung bypass machine is an extremely useful tool, however, using it is not without risk and it often takes patients many weeks to recover after an open heart operation.

Recent advances in technology have introduced new replacement valves which can be ‘injected’ into position with the heart still beating (avoiding the need to use the heart-lung bypass machine) and without a need for the surgeon to expose all the heart. However, the new valve has not been extensively studied and has been used in around 300 patients worldwide so far. Surgeons have reported their experiences but only for small numbers of patients and without comparing their experiences directly with the conventional replacement valves.

InVITe will investigate the effectiveness of injectable pulmonary valve replacement compared to standard pulmonary valve replacement. Patients will be allocated at random (by chance) to receive either the “injectable” valve or standard valve. We will follow patients to determine whether the use of injectable valves results in quicker recovery and shorter stay in hospital and is cost saving for the NHS. We will also determine whether these valves function as well as the conventional ones.

 

 

Contact Information

Chief InvestigatorMr Andrew Parry, Consultant Paediatric Cardiac Surgeon, Bristol Royal Hospital for Children 

Study coordinator: Rachael Heys

E-mail:  invite-trial@bristol.ac.uk

 

Outcome Monitoring After Cardiac Surgery (OMACS)

Sponsor: University Hospitals Bristol 

Status: Ongoing

After cardiac surgery, patients routinely have a follow-up appointment six weeks after discharge. After this appointment the patient is usually referred back to the care of their general practitioner (GP) and no longer receives care from, nor is followed up by, the cardiac surgery team. This means that we have little information about their long term health.  This study will allow long-term data collection after cardiac surgery.

The aim of OMACS is to collect information about the medium and long-term health status of patients who have had cardiac surgery.

We will ask participants to complete a questionnaire relevant to the surgery they have received and / or a quality of life questionnaire at 3 months and 12 months post-operatively.

Participants will be given a choice of participating electronically or via post to maximise the convenience for participants.

We will ask potential participants for consent to use their data collected as part of their clinical care at this hospital (Bristol Royal Infirmary) or at other hospitals using nationally collected data (called Hospital Episode Statistics or HES).

OMACS will also investigate whether the presentation style and format of the information leaflets provided to potential participants has an effect on the consent rates to the study.

This information will be used to help us design future research and answer research questions in ongoing studies.

Contact Information

Chief Investigator: Dr Lucy Culliford, Research Fellow

Study coordinator: Dr Lucy Culliford

E-mail:  omacs-study@bristol.ac.uk

 

Role of potassium channels in sustaining physiological responses of human resistance arteries

Funder: British Heart Foundation 

Sponsor: University of Oxford 

Status: Recruiting

The way arteries in the heart constrict and dilate is important for controlling the blood flow through them.  This process is disrupted in people with coronary artery disease, leading to heart attack and strokes.  We want to understand how the diameter of coronary arteries is controlled normally and how this changes in diseased arteries, which are lined with fatty deposits (plaque).  

In the Oxford Artery study we are recruiting patients undergoing heart valve operations (who have normal arteries) and asking them to donate the piece of tissue from the heart that gets removed during surgery and is normally discarded.  We are conducting laboratory experiments on the arteries found in these pieces of heart tissue.  We want to establish how electrical events within the wall of these arteries control their diameter and therefore the blood flow through them.  This research may lead to new treatments for people with coronary artery disease. 

The research is being carried out at Oxford University and we are assisting by recruiting patients and providing samples and clinical data.

Contact Information

Chief Investigator: Dr Kim Dora

Study coordinator: Rachael Heys

E-mailoxford-artery-study@bristol.ac.uk

 

Unit Role: Recruiting Centre

The PROVE study is run by the University of Bristol.  They believe that some elements of stem cells, (which are present in bone marrow) also exist in arteries and veins.  These cells are potentially useful as they could be used to form new arteries and thus improve the circulation of patients suffering from coronary heart disease.

Veins of the leg or arteries of the arm are used during CABG surgery.  The surplus of these vessels is discarded at the end of the operation so we are asking patients if we can use them to study if they contain the original cells capable of forming new arteries.

  • Patients with more than one vessel disease having CABG+/valve are approached to take part in this research
  • Observational trial so patients can participate in PROVE and another study

Contact Information

Research Nurse: Emma Hopkins 

 

The Renoprotective value of Leukodepletion in Heart Valve surgery: an external feasibility randomised controlled trial

Funder: NIHR/RfPB 

Sponsor: University Hospitals Bristol 

Status: Analysis 

 People who have surgery to repair damaged heart valves can suffer damage to their kidneys after their operation. This damage is caused by the heart-lung bypass machine, which takes over the job of pumping blood around the body whilst the heart is being operated on. The white blood cells (leukocytes) circulating in the blood react to the materials in the heart-lung bypass machine, which ‘activates’ them and causes inflammation throughout the body. This inflammation can damage the kidneys. 

The ROLO study is looking to see if removing the ‘activated’ white blood cells from the blood (through a special filter in the heart-lung bypass machine) during surgery will reduce damage to the kidneys. Patients undergoing heart valve operations were allocated by chance to having their blood filtered using either a standard filter, which doesn’t filter out the white blood cells, or a new filter, which filters the blood in the same way as the standard filter, but also filters out the white blood cells.

Participants were followed-up for three months after surgery to see if they developed kidney injury.

Participants were recruited from Blackpool Teaching Hospitals NHS Foundation Trust. CTEU Bristol has been contracted to provide trial and data management services for the study, including the statistical analyses.

The study is now closed and the final report has been submitted to the funder

Department of Health Disclaimer: The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the RfPB, NIHR, NHS or the Department of Health.

Contact Information

Study coordinator: Lucy Dabner

E-mailrolo-trial@bristol.ac.uk

 

Preoperative Volume Replacement vs. usual care in Diabetic patients having CABG surgery: a randomised controlled trial

Diabetes mellitus is a major risk factor for complications in patients having coronary artery bypass graft (CABG) surgery. Such complications pose a serious threat to patients and prolong intensive care and hospital stay. Renal failure is more common after coronary artery bypass grafting in diabetics than in non-diabetics. Volume depletion is associated with a low glomerular filtration rate, and may lead to acute renal impairment/failure. 

Preoperative volume replacement therapy is reported to increase the glomerular filtration rate and we hypothesised that this would reduce renal impairment.

VeRDiCT was designed to test whether diabetic patients randomised to pre-operative volume replacement would have less problems with renal impairment after surgery. The study recruited patients from the Bristol Royal Infirmary, and ran in parallel with a study in India.

Patients who consented to take part in VeRDiCT were allocated to either standard care or to volume replacement therapy, which meant receiving an intravenous drip of Hartmann’s solution for about 12 hours before their operation. Standard care meant that the patients only had volume replacement if it was needed for another clinical reason. Numerous samples of blood and urine were collected during the patient’s stay in hospital and information about the patient’s health on the day that they left hospital was recorded. Patients were followed up by telephone call 6-8 weeks after surgery to assess their wounds and answer questions regarding readmissions, and then again by questionnaire 3 months after surgery to assess their health status and health resource usage.

Recruitment went well and the data is being prepared ready for statistical analysis. The results are expected in the Summer of 2017.

The study was funded by the Garfield Weston Trust (Ref: PMS/MMS-07/08-3001), and supported by the NIHR Bristol Cardiovascular Biomedical Research Unit and the British Heart Foundation.

The VeRDiCT protocol paper has been published, and can be read here

Contact Information

Chief InvestigatorProf Raimondo Ascione

Trial Co-Ordinator: Maddie Clout

E-mailverdict-trial@bristol.ac.uk

 

Unit Role: Recruiting Centre

Sponsor: Vascular Graft Solutions Ltd

Coronary artery bypass grafts (CABGs) are well-established as the best treatment for those with multiple diseased coronary vessels. Most people undergoing CABG require more than one graft, to both the left and right side of the heart.

The standard operation (80-90% of patients ) is to use one of the mammary arteries and a saphenous veins (SVG) from the leg or radial artery from the arm. CABG provides excellent short and medium term success, but its long-term success may be limited by failure of the vein grafts. Ten years after CABG, around half of vein grafts have become diseased / blocked, although current drug therapy – such as aspirin and statins – may reduce this failure. Blocked / diseased grafts means that the patient may develop recurrent angina and may require further treatment / possibility of a re-do op.

The ‘VEST’ is a delicate braided wire ‘sleeve’ which is threaded over the bypass vein graft, during the operation. The device remains in place forever, providing external support to the vein graft, in-order to prevent it from becoming deformed. Research to date has shown that using the device may improve the condition of the graft over time. The Vest devices are approved and being commercially used in Europe and Israel.

The aim of the study is to enhance the clinical data available for use of the ‘VEST’ in bypass grafts and obtain long-term data. It is currently in use in UK and Europe and has been previously used in two clinical studies, too. However, more evidence and data need to be collected and this is the reason for performing this study. The patients in the study will have consented to have a follow up CT scan at 6 months and an angiogram at 2 years post cardiac surgery, in order to assess the patency and uniformity of the saphenous vein graft with the VEST sleeve, when compared with the vein without the VEST sleeve.

Hopefully data from this trial will give a better picture of the long term performance of the VEST product.

Contact Information 

Research Nurse: Emma Hopkins

 

Prospective, randomised, controlled investigation comparing the safety and performance of 032-11 surgical haemostat 2g applicator with FLOSEAL hemostatic matrix as an adjunctive haemostat in cardiac surgery and thoracic surgery 

Sponsor: Medtrade

Unit Role: Recruiting Centre

In surgery, some degree of haemorrhage is unavoidable.  When the body is under shock and stress haemostasis can be harder to achieve, and can also be impaired by some drugs (eg. heparin or aspirin) or surgical procedures (eg. induced hypothermia).  Techniques for maintaining haemostasis in surgery include mechanical (direct pressure, sutures and staples), thermal (electro-cautery and laser), and chemical (pharmacotherapy, topical sealants/adhesives and topical haemostats).

The Victory study is a prospective, randomised, controlled investigation comparing the safety and performance of 032-11 Surgical Haemostat Applicator with FLOSEAL® Haemostatic Matrix as an adjunctive haemostat in cardiac surgery and thoracic aortic surgery.

  • 032-11 is a chitosan (crustacean animal derived) based haemostat
  • 032-11 does not interact with the blood clotting cascade which may be advantageous in coagulopathic patients
  • When activated, a gel patch is formed which acts as a physical barrier to blood loss, and can be absorbed by the body enabling closure of the surgical site without removal of the product
  • If adjunct haemostat required during surgery (post CPB), patients randomised to 032-11 or FLOSEAL ® (Market leading haemostat in the UK)
  • 200 patients to be randomised over 9 sites
  • Commercial trial, study sponsor is called Medtrade
  • Randomised patients are followed up at their routine outpatient appointment

Contact Information 

Research Nurse: Emma Hopkins