Intensive Care Current Research

GuARDS is a research study running in Intensive Care Units (ICU) across the UK.

Patients with Acute Respiratory Distress Syndrome (ARDS) and the treatment being tested is a safe drug called dexamethasone alongside the standard ICU care.

PI: Dr Matt Thomas

Planned end date: 31st July 2027

Local ref: 5505

SepTiC is the name of a research trial which is looking at treatments for sepsis. The trial aims to find out what are the best treatments for sepsis.

We are testing three different things in this study:

1. Diagnostic Trial 

Patients who have sepsis due to a serious infection need treatment as soon as possible. The treatment usually starts with drugs such as antibiotics to help fight the infection. Sometimes these drugs are used for longer than needed, which can cause side effects that can be harmful to patients. This might also make infections more difficult to treat in the future as it risks bugs (bacteria and other microorganisms) becoming used to and not being killed by antibiotics. Also, not all patients who are at first thought to have sepsis (and receive antibiotics) have an infection, so they may not have required antibiotic treatment at all. So, it is really important that we find out which patient needs antibiotics for an infection, who does not need them and if we can stop them, as soon as possible.   

2. Fluid Trial

Giving fluids, through tubing in the arm known as a ‘drip’, is standard practice in treating sepsis, but there is no clear guide on how much fluid is enough or too much, and so a build-up of fluid in the body can occur which may be harmful.  We will test how much fluid should be given and whether to remove any build-up of extra fluid.

For patients in this group, depending on their condition, we will give as little fluid as possible and, when safe, will treat any build-up of fluid which has occurred using medications called diuretics. If the patient is already receiving kidney dialysis, we will use this to remove excess fluid instead of diuretic medications.

3. GM-CSF Trial

GM-CSF is the short name for granulocyte-macrophage colony-stimulating factor.  This is approved in the USA by the FDA as type of protein that helps to make more white blood cells to help the immune system fight infection. The GM-CSF used in this trial is called Sargramostim.

This treatment will only be given to patients who need support for their breathing or other important organs. For patients in this group, an injection under the skin of 250-500mcg Sargramostim is given once a day for up to 8 days.  To help test if this does help patients, they will be compared with other patients who will have a sugar solution made to look the same as the drug.  This is also given once a day for 8 days.  This is known as a ‘placebo’.

PI: Dr Matt Thomas

Planned end date: 30th April 2027

Local ref: 5688

We wish to investigate whether giving deceased organ donors a single dose of the commonly prescribed drug, Simvastatin, is beneficial for transplant recipients.

All donated organs have suffered some damage. As the brain dies chemicals are released which cause an “inflammation” of the body. Measurements of this “inflammation” link to how well the organs function after transplant.  We know that statins have many benefits, including dampening down inflammation in the body and individual organs. 

Doctors in Finland linked this information in a clinical study. Organ donors, donating their heart, were randomised to receive a statin. The recipients who received a heart from a donor who had statins had less heart damage.  This was a small study but there was a small benefit for lung and liver recipients and no disadvantage in receiving any organ from a donor who had received the drug.   

A significant number of organs offered for transplant are not used; for the heart, this figure is about 75%.  The reason for being so selective is that poor function of the donor heart in the recipient is the most common cause of death after a transplant. Any step in the donor which might improve the transplanted heart, or other organ, could have a major benefit to the recipient.

We plan to enrol 650 adult brain dead donors across the UK per year in a randomised controlled trial.  Half the donors will receive Simvastatin in addition to standard care, compared to standard care only.  The drug will be given after the donor family have consented to both organ donation and involvement in research.  

Half of the recipients will receive a heart from a donor given the drug. We will follow the results of transplant, using data already collected in the national transplant database. No extra data or blood samples will be needed.

Project Details
Principal Investigator: TBC
Planned End Date: TBC
Local Ref: 4145

Randomised trial of the clinical and cost effectiveness of a supraglottic airway device versus intubation during in-hospital cardiac arrest.

A multi-centre, open label, pragmatic, individually randomised, parallel group, superiority trial and economic evaluation to determine the clinical and cost effectiveness of a supraglottic airway versus tracheal intubation during in-hospital cardiac arrest. The trial will include an internal pilot to confirm feasibility.

Chief Investigator – Professor Jonathan Benger

Principal Investigator – Dr Jasmeet Soar

Traumatic brain injury (TBI) is a leading cause of death and long-term disability. Approximately half of those with severe traumatic brain injury will be severely disabled or dead 6 months post injury. Given the young age of many patients with severe TBI, the economic and more importantly the social cost to the community is very high.

Management of patients with brain injuries focusses on the prevention of “secondary” brain injury. This can result from complications of the injury such as insufficient blood flow, or insufficient oxygen in the brain. The mainstay of preventing secondary injury has been the management of patients in the intensive care unit (ICU), with treatment aimed at minimising any rise in intracranial pressure (ICP) and maintaining blood flow. However, rises in ICP may be a late indicator of secondary injury

The brain depends on an uninterrupted supply of oxygen and monitoring the oxygen levels in brain tissue may provide a more useful marker of secondary injury. Several small trials have provided some promising results to support the use of monitoring and optimising brain tissue oxygenation to minimise secondary brain injury.

There have been no robust clinical trials to provide evidence to support the use of this technology. Clinicians are uncertain about the benefit of monitoring brain tissue oxygen levels. This important question would be answered by a trial testing this strategy compared to the standard management of monitoring ICP alone.

The BONANZA trial will enrol 860 patients who have suffered a severe TBI and require ICP monitoring. Each patient will be randomised to either a brain tissue oxygen monitoring strategy (including ICP monitoring) or the standard strategy of ICP monitoring alone. Functional and neurological recovery will be assessed at 6 months post injury to see if there is a difference between both groups of patients.

PI: Dr Matt Thomas

Planned end date: 1st December 2026

Local ref: 5381

GENOMICC - Genetics Of Mortality In Critical Care

The study will work within the International Severe Acute Respiratory Infection Consortium and International Forum of Acute Care Trialists, two global initiatives , to establish a prospective DNA resource for hypothesis-testing and genome-wide discovery of host genetic variants underlying susceptibility to severe infection, and outcome from life-threatening systemic injury. We will: Obtain a single DNA sample from patients with:

1. Susceptibility to severe disease;
2. Susceptibility to specific outbreaks and exposures of public health interest;
3. Susceptibility to death following onset of severe illness due to specific syndromes,

And;

4. Susceptibility to death from quantifiable sterile injury.

Obtain DNA from the parents of patients with extreme susceptibility to eligible syndromes (those under 40 and free from significant comorbidity).

Obtain DNA samples, where possible, from appropriate comparison or control groups.

Combine existing DNA resources in a virtual collaborative network to enable rapid hypothesis-testing of candidate variants.

Establish and continually replenish a small cohort of individuals with known profound susceptibility to specific pathogens, who will be invited to provide repeat samples for in vitro studies of cellular responses to relevant stimuli.

Where appropriate and implementable, allow return of clinical relevant information to the NHS regarding participants.

Allow lifetime linkage (and beyond) to healthcare and other relevant data (including registries, healthcare records, research datasets, and lifestyle and other data).

Chief Investigator – Professor JK Baillie

Principal Investigator – Dr Matt Thomas

MARCH - Mucoactives in Acute Respiratory failure: Carbocisteine and Hypertonic saline.

When patients are critically ill, one of the main complications is called ‘acute respitatory failure’. This is when the patient’s illness causes their lungs to fail to work. Patients need to be admitted to the Intensive Care Unit and often need to have a breathing machine, or ventilator, to help them breathe and ensure that enough oxygen gets into their blood.

However, one problem that can occur as a result of being on a ventilator, is difficulty clearing secretions from the lungs. This can happen for a number of reasons. Lack of the body’s own natural moisture in the airways can make the secretions become very thick and dry. The breathing tube from the ventilator can also make coughing up secretions more difficult. Patients may also feel too sleepy from their medication to cough by themselves. Not being able to clear secretions from the lungs can make breathing harder, and this may result in developing a lung infection.

To reduce the problem of thick secretions, the air coming from the ventilator can have moisture added to it. Other treatments can include using a suction tube to remove secretions via the breathing tube. Physiotherapists may also use techniques to help clear secretions. In some cases, medications called ‘mucoactives’ may be prescribed for patients. However, even though mucoactive medications are commonly used in patients with lung failure in the ICU, we do not know if these medications really help patients when they have thick secretions that are difficult to clear.

The aim of this study is to determine whether use of mucoactives in critically ill patients with acute respiratory failure improves outcomes and is cost effective, compared to usual airway clearance management. The study objectives are to conduct a large, UK, multi-centre, pragmatic, randomised controlled trial to:

1. Determine the clinical effectiveness of two mucoactives (carbocisteine or hypertonic saline), or a combination of both, on duration of mechanical ventilation (primary outcome), and a range of secondary clinical and safety outcomes.
2. Estimate, in an integrated economic evaluation, the cost-effectiveness of the mucoactives.

Chief Investigator – Professor Danny McAuley

Principal Investigator – Dr Matt Thomas