Critical illnesses including acute respiratory disease syndrome and pandemic infection Respiratory
Conditions
Interventions
Simvastatin:
Simvastatin may help repair the lungs by reducing inflammation and repairing the blood vessels in the lungs. Simvastatin will be administered at a dose of 80 mg once daily via the entera
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Critically ill patients in hospital and at least one of the following: 1.1. ARDS 1.2. A pandemic-associated syndrome* *This will be triggered if a pandemic is declared ARDS as defined by: 1. A known acute clinical insult or new or worsening respiratory dysfunction, and 2. Receiving respiratory support via invasive mechanical ventilation or non-invasive ventilation including continuous positive airway pressure, or high-flow nasal oxygen =30L/min and 3. Within the same 24-hour time period: 3.1. Bilateral opacities on chest imaging not fully explained by effusions, lobar/lung collapse/atelectasis, or nodules, and 3.2. Respiratory failure not fully explained by cardiac failure, fluid overload, pulmonary embolism, acute airways disease, or interstitial lung disease and, 3.3. PaO2/FiO2 ratio <40 kPa from arterial blood gases, or SpO2/FiO2 <315 from pulse oximetry where SpO2 <97. The time of onset of ARDS is when the last criterion in 3 is met.
Exclusion criteria
Exclusion criteria: 1. >48 hours from diagnosis of ARDS 2. Planned withdrawal of life-sustaining treatment within the next 24 hours 3. Previous enrolment in the PANTHER trial in the last 12 months 4. Declined consent 5. Aged <18 years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 28-day organ support-free days, incorporating mortality as a composite on an ordinal scale. Organ support is defined as needing either respiratory or cardiovascular support | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Progression to invasive mechanical ventilation, extracorporeal membrane oxygenation or death among those not receiving that support at baseline 2. 28-day vasopressor-free days 3. 28-day respiratory support–free days 4. Receiving new renal replacement therapy 5. ICU length of stay 6. Hospital length of stay 7. All-cause mortality at 28 and 90 days 8. Safety outcomes: 8.1. Elevated Creatine Kinase more than 10 times the upper limit of normal 8.2. Alanine Transaminase or Aspartate Transaminase or both more than 8 times the upper limit of normal 8.3. Serious infection, defined as positive blood cultures requiring treatment and positive pulmonary aspergillosis requiring treatment 8.4. Venous thromboembolism 8.5.Stroke 8.6. Myocardial infarction 8.7. Ischaemic bowel 8.8. Gastrointestinal perforation 8.9. Clinically important gastrointestinal (GI) bleeding confirmed on upper endoscopy 9. Serious adverse events 10. Physical function measured using Short Physical Performance Battery (SPPB) at hospital discharge (up to 1 week prior to discharge) 11. Cognitive impairment measured using the Montreal Cognitive Assessment (MoCA) at hospital discharge (up to 1 week prior to discharge) Tertiary outcome measures: 1. 14-day delirium and coma-free days* 2. Incidence of ICU-acquired weakness (MMST and hand grip strength dynamometry and maximal inspiratory) at day 7 and ICU discharge* 3. Health-related quality of life (EQ-5D-5L), Hospital Anxiety and Depression Scale (HADS), Social and Wellbeing (SF-36), Impact of Events Scale (6 item), care and wellbeing needs and cognitive impairment (MoCA) at 90 days and 180 days* *Not all sites are expected to collect these endpoints 90 days from randomisation is the final endpoint | — |
Countries
England, United Kingdom
Outcome results
None listed