Clinical Research in Critical Care

Current Research | Transfuse

 

TRANSFUSE-RCT

Transfuse

(STandaRd Issue TrANsfusion versuS Fresher red blood cell Use in intenSive carE (TRANSFUSE) – a randomised controlled trial)

TRANSFUSE-RCT is a multi-centre, randomised, controlled trial, testing the effect of the freshest available red blood cell (RBC) unit compared to standard practice, on mortality in critically ill patients who require RBC transfusion.

RBC transfusion is a very common and potentially life-saving treatment in intensive care units (ICUs). However, RBC transfusion has also been associated with an increased risk of morbidity and/or mortality in critically ill patients. Although this association may reflect a variety of factors, attention has increasingly focused on the possible adverse impact of transfusing RBCs stored for a prolonged time, and have developed a so called "storage lesion". The term "storage lesion" refers to the fact that during the 42-days storage, in a way that increases over time, red cells develop important biochemical and structural derangements. These age-related changes in transfused RBCs may have important clinical consequences.

The hypothesis is that in critically ill patients who require a RBC transfusion, compared to standard practice, administration of the freshest available compatible RBC decreases 90-day patient mortality. Patients will be randomised to either the "Freshest available blood group" or the "Standard care group". Freshest available blood group: These patients will receive the freshest available group-specific compatible RBC unit in the transfusion service. Standard care group: These patients will receive standard practice, which is the oldest available group-specific compatible RBC unit in the transfusion service.

To guide blood transfusion policy rationally and nationally, we will test freshest available RBC versus standard practice (older blood) in critically ill patients in a definitive large multicenter RCT, using the established network of contributing hospitals.

This will be a collaboration between Intensive Care Units (ICUs) in the Irish Critical Care -Clinical Trials Group (ICC-CTG) and the Australian and New Zealand Intensive-Care Society- Clinical Trials Group (ANZICS-CTG) to determine whether, compared to standard care, transfusion of the freshest available allogenic red blood cells (RBC) decreases patient mortality.

This study is supported by the Irish Blood Transfusion Service and the Australia Blood services and will be overseen by collaboration between the ICC-CRC and the Australian and New Zealand Intensive Care- Research Centre

FAQ

What is a storage lesion?

Storage of RBCs in a preservative medium is associated with metabolic, biochemical and molecular changes to erythrocytes referred to as “the storage lesion”. These age-related changes in transfused RBC may have important clinical consequences.

How does it work?

Eligible patients who require a blood transfusion will be randomised by the ICU team using a web based system. The study number generated at randomisation will be conveyed to the transfusion service by telephone and on the blood request slip. The hospital transfusion service will allocate the appropriate blood to the patient as designated by a randomisation schedule. Allocation will be either standard practice (the oldest compatible available blood, front of fridge) or freshest compatible available (back of fridge). The patient will continue to receive the randomised treatment arm for any additional blood transfusion episodes during their hospital stay. A telephone follow-up will be conducted at 90 and 180days.

Inclusion Criteria?

ICU patients or emergency department patients accepted for ICU admission, with an anticipated ICU stay of at least 24 hours, in whom the decision has been made by medical staff to transfuse at least one RBC unit.

Exclusion Criteria?

  • Age younger than 18? year
  • Previous RBC transfusion during the current hospital admission (including transfusion in another hospital for transferred patients)?
  • Diagnosis of transplantation or hematologic malignancy?
  • Pregnancy?
  • Cardiac surgery during the present hospital admission?
  • Expected to die imminently (<24hrs)?
  • The treating physician believes it is not in the best interest of the patient to be randomised in this trial
  • Known objection to the administration of human blood products?
  • Participation in a competing study.

Current Research | PHARLAP-RCT

 

PHARLAP-RCT

Pharlap

(Permissive Hypercapnia, Alveolar Recruitment and Limited Airway Pressure – Randomised Controlled Trial)

The PHARLAP-RCT is a prospective, multi-centre, randomised controlled trial of the clinical efficacy of a ventilation strategy (called PHARLAP) compared to standard mechanical ventilation in acute respiratory distress syndrome (ARDS). This trial will be collaboration between Intensive Care Units of the Irish Critical Care- Clinical Trails Group (ICC- CTG) and the Australian and New Zealand Intensive Care Society- Clinical Trials Group (ANZICS-CTG).


ARDS is an inflammatory condition of the lung parenchyma. ARDS is a global problem and despite best supportive care, ARDS is common and associated with significant mortality and morbidity. Any intervention that could potentially impact mortality, time on mechanical ventilation and the need for expensive rescue therapies would have important human, social and financial benefits and warrant investigation.

The study will investigate the clinical efficacy of the PHARLAP strategy compared to standard mechanical ventilation in ARDS patients. In a prospective, multi-centre, randomised controlled trial 340 adult patients in total will be enrolled who have developed ARDS within the past 48 hours and randomly allocate them to either the PHARLAP or a control ventilation strategy.

FAQ

Inclusion Criteria?

ICU Patients ≥16 years of age who are i) intubated, ii) within 48 hours of a diagnosis of moderate or severe ARDS based on the Berlin Consensus Conference Criteria (PaO2/FiO2 <200 mmHg) on over 5 cmH2O of PEEP and ii) have received ≤ 5 days of invasive mechanical ventilation.

Exclusion criteria?

  1. Barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema or the presence of any intercostal catheter)
  2. Significant chest trauma i.e. multiple rib fractures
  3. Active bronchospasm or a history of significant chronic obstructive airway disease or asthma
  4. Moderate and severe traumatic brain injury, the presence of an intracranial pressure monitor, or any medical condition associated with a clinical suspicion of raised intracranial pressure
  5. Unstable cardiovascular status defined as sustained heart rate < 40 or > 140 bpm, ventricular tachycardia, SBP < 80 mmHg despite significant vasopressor support
  6. Lack of consent (treating physician or next of kin)
  7. Inevitable and imminent death
  8. Pregnancy
  9. Receiving ECMO.

Current Research - PEPTIC

 

PEPTIC

Peptic

Proton Pump Inhibitors vs. Histamine-2 REceptor Blockers for Ulcer Prophylaxis Therapy in the Intensive Care Unit

Multi-centre, cluster crossover, randomised trial comparing proton pump inhibitors (PPIs) with histamine-2 receptor blockers (H2RBs) for ulcer prophylaxis in mechanically ventilated ICU patients. The overall objective of this study is to establish the risk of in-hospital deathusing PPIs vs. H2RBs for routine ulcer prophylaxis in mechanically ventilated patients in the ICU. Cluster crossover trial using data from existing databases and registries.

Between 13 and 20 million patients are admitted to an ICU around the world each year. Of these patients, 18- 30% die during their ICU admission. Almost all of the patients who die in the ICU receive mechanical ventilation. Despite this tremendous mortality burden, no treatment has been proven to reduce mortality in a large-scale trial in a general population of critically ill patients who require mechanical ventilation.

FAQ

Inclusion Criteria?

Any non-paediatric ICU that routinely manages mechanically ventilated patients will potentially be eligible to participate in the study.

Exclusion Criteria?

ICUs that are unable or unwilling to follow the trial protocol, or?ICUs that are unable to capture the required study data from established databases (potential study centres will be required to demonstrate that they are able to obtain required data from existing data sources by participating in a retrospective cohort study using the study data points.

Current Research | SPICE - III RCT

 

SPICE III RCT

SPICE

Sedation Practices in Intensive Care Evaluation: SPICE III: A Prospective Multicentre Randomised Controlled Trial of Early Goal-Directed Sedation Compared with Standard Care in Mechanically Ventilated Patients in Intensive Care

A prospective, un-blinded, randomised controlled trial of Early Goal-Directed Sedation (EGDS) compared with standard care. The study will recruit patients who are intubated and ventilated in a participating ICU, are expected to remain intubated the day after enrolment and need immediate and ongoing sedation.

Over the last decade clinical practice has changed somewhat towards the use of lighter levels of sedation whenever clinically safe, better management of pain, and?recognition of delirium as occurring commonly in patients with critical illness.?A number of studies suggest that the centrally mediated alpha­2 agonist sedative dexmedetomidine facilitates rousable sedation, shortens ventilation time, and attenuates the occurrence of delirium, and may therefore be advantageous compared to other sedatives. Whether these potential advantages are associated with improvement in patient­centred outcomes, such as long­term mortality and cognitive function, is unknown.

The primary aim of this study is to determine whether Early Goal-Directed Sedation, compared to standard care sedation, reduces 90-day mortality in critically ill patients who are expected to require mechanical ventilation for longer than 24 hours.

The study will compare a strategy of early titrated light sedation (early goal directed sedation) to standard sedation practices in critically ill patients ventilated for >24 hours. The primary aim of this study is to determine whether Early Goal­Directed Sedation, compared to standard care sedation, reduces 90­day mortality in critically ill patients who are expected to require mechanical ventilation for longer than 24 hours. The study is an international multi­centre trial which in total will recruit 4000 patients.

FAQ

Inclusion Criteria?

Subject has been intubated and is receiving mechanical ventilation, the treating clinician expects that the patient will remain intubated until the day after tomorrow (unlikely to be extubated the following day) and the patient requires immediate ongoing sedative medication for comfort, safety, and to facilitate the delivery of life support measures.

Exclusion Criteria?

  • Age less than 18 years
  • Patient is pregnant and/or lactating
  • Has been intubated (excluding time spent intubated within an operating theatre or transport) for greater than 12 hours in an intensive care unit?
  • Proven or suspected acute primary brain lesion such as traumatic brain injury, intracranial haemorrhage, stroke, or hypoxic brain injury
  • Proven or suspected spinal cord injury or other pathology that may result in permanent or prolonged weakness?
  • Admission as a consequence of a suspected or proven drug overdose or burns
  • Administration of ongoing neuromuscular blockade
  • Mean arterial blood (MAP) pressure that is less than 50 mmHg despite adequate resuscitation and vasopressor therapy at time of randomization
  • Heart rate less than 55 beats per minute unless the patient is being treated with a betablocker or a high grade atrio­ ventricular block in the absence of a functioning pacemaker
  • Known sensitivity to any of the study medications or the constituents of propofol (egg, soya or peanut protein)
  • Acute fulminant hepatic failure?
  • Patient has been receiving full time residential nursing care
  • Death is deemed to be imminent or inevitable during this admission and either the attending?physician, patient or substitute decision maker is not committed to active treatment

Current Research | Point Prevalence Programme

This program acts as an observational study, without any intervention, and involves collecting data on topics of interest, in patients in multiple intensive care units, on a specific day or days. It provides no information on outcomes, but provides very important information on how common a problem is, and what is currently being done to manage that problem. This is an ongoing program consisting of multiple research collection days, each performing multiple, independent studies simultaneously, including a number of paediatric studies.

Design:

The Point Prevalence studies are purely observational, and no intervention is required by the study protocol. The collected data will be entered via a secure password-protected encrypted website (RedCAP).

Methods: 

This project is a prospective, observational, multicentre, single-day, point prevalence study of evidence based processes of care using piloted CRF. Research coordinators from each participating institution collect data on all patients who are present in the ICU on the study day. Only fully de-identified data is released to the program’s management centre.

Previous Research | ARISE

Background Synopsis

The ARISE RCT was a multi-centre, randomised controlled trial of the effect of early goal-directed therapy, compared to standard care, on 90-day mortality in patients presenting to the Emergency Department with severe sepsis.

Patients were randomised in the ED to receive either EGDT for a total of 6 hours post-randomisation, or standard care. Patients assigned to receive EGDT were cared for by the dedicated ARISE study team. The patient received treatment as per the study protocol for 6 hours with central blood oxygen levels as the target end-point, and then received standard care. Patients assigned to receive standard care continued to be cared for by the hospital team in accordance with current best practice. Patients in both groups received any additional treatment needed, such as antibiotics or surgery.

The study was conducted in multiple sites with 1600 patients enrolled in the study over a 2.5 year period.

Results:

Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.

Conclusions:

In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. [More]

Previous Research | HARP-2

Background Synopsis

(Hydroxymethylglutaryl- CoA reductase inhibition in Acute lung injury to Reduce Pulmonary dysfunction - a multi-centre RCT)

Studies in animals and in vitro and phase 2 studies in humans suggest that statins may be beneficial in the treatment of the acute respiratory distress syndrome (ARDS). This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS.

Methods

In this multicenter, double-blind clinical trial, we randomly assigned (in a 1:1 ratio) patients with an onset of ARDS within the previous 48 hours to receive enteral simvastatin at a dose of 80 mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator-free days to day 28. Secondary outcomes included the number of days free of nonpulmonary organ failure to day 28, mortality at 28 days, and safety.

Results

The study recruited 540 patients, with 259 patients assigned to simvastatin and 281 to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P=0.21) or days free of nonpulmonary organ failure (19.4±11.1 and 17.8±11.7, respectively; P=0.11) or in mortality at 28 days (22.0% and 26.8%, respectively; P=0.23). There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug. [More]