Plain English Summary
Background and study aims
Many different circumstances, such as severe infection or an accident, may result in a person becoming critically ill. For reasons that are unclear, when people are critically ill, their brain function is often impaired – a condition of severe confusion called delirium. Delirium is common, affecting up to two out of every three patients in intensive care units (ICU), and results in a longer hospital stay and a higher risk of death. Importantly, after recovery from the initial illness, following delirium, patients frequently go on to experience the equivalent of a mild or accelerated dementia. There is no proven effective treatment for delirium. It is thought that delirium is often a result of inflammation in the brain. Simvastatin, usually used to reduce cholesterol, has been shown to have significant anti-inflammatory properties. The aim of this study is to test the effectiveness of simvastatin at reducing delirium in the critically ill.
Who can participate?
Patients aged over 18 requiring mechanical ventilation (a machine to support breathing) within 72 hours of admission to intensive care.
What does the study involve?
Patients will be randomly allocated to be given either simvastatin or a dummy drug (placebo). We will count the number of days a patient is delirious, how fast they recover and how well their brain functions at 6 months using a telephone questionnaire.
What are the possible benefits and risks of participating?
Simvastatin is a safe, well-tolerated drug. If simvastatin reduces delirium it would likely decrease ICU stay. Demand for ICU exceeds supply and a treatment that reduced use of ICU resources would result in increased availability of facilities for critically ill patients. The potential impact of an effective treatment for delirium is considerable.
Where is the study run from?
Watford General Hospital (UK).
When is the study starting and how long is it expected to run for?
February 2013 to January 2015.
Who is funding the study?
National Institute for Health Research (UK).
Who is the main contact?
Dr Valerie Page
valerie.page@whht.nhs.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Valerie J Page
ORCID ID
Contact details
60 Vicarage Road
Watford
WD18 0HB
United Kingdom
-
valerie.page@whht.nhs.uk
Additional identifiers
EudraCT number
2012-003114-13
ClinicalTrials.gov number
Protocol/serial number
13988
Study information
Scientific title
Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in mechanically ventilated patients at high risk of delirium: a randomised double-blind placebo controlled trial
Acronym
MoDUS
Study hypothesis
Delirium is common affecting up to 2 out of every 3 patients in ICU, and results in a longer hospital stay and a higher risk of death. Importantly, after recovery from the initial illness, following delirium, patients frequently go on to experience the equivalent of a mild or accelerated 'dementia'. There is no proven effective treatment for delirium. It is thought that delirium is often a result of inflammation in the brain. Simvastatin, usually used to reduce cholesterol, has been shown to have significant anti-inflammatory properties. This study is a randomised, double-blind, placebo controlled trial. 142 patients will randomly allocated to be given either simvastatin or a placebo. Outcomes include number of days a patient is delirious, how fast they recover and cognitive function at 6 months using an approved telephone questionnaire. If simvastatin reduces delirium it would likely decrease ICU stay. Demand for ICU exceeds supply and a treatment that reduced use of ICU resources would result in increased availability to appropriate facilities for critically ill patients. This study is being funded by a Research for Patients Benefit Grant and run in partnership with ICUSteps and the Alzheimer's Society.
More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13988
Ethics approval
NRES Committee North East - Newcastle & North Tyneside 1, 06/12/2012, ref: 12/NE/0383
Study design
Randomised double-blind placebo-controlled trial, Design type: Prevention, Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Generic Health Relevance and Cross Cutting Themes; Subtopic: Generic Health Relevance (all Subtopics); Disease: Critical Care
Intervention
Simvastatin 80 mg or placebo daily for up to 28 days
Intervention type
Drug
Phase
Not Applicable
Drug names
Simvastatin
Primary outcome measures
Alive, delirium free and coma free days; Timepoint(s): 14 days
Secondary outcome measures
1. Incidence of delirium
2. Delirium/coma free days in first 28 days
3. Number of ventilator free days at 28 days
4. Length of critical care and hospital stay
5. Mortality at 6 months; (f) Organ failure free days
6. Cognitive Impairment at 6 months
7. Health related quality of life over the 6 month study period using the EQ-5D-5L
8. Quality adjusted life years at 6 months
9. Healthcare resource use and associated costs over the 6 month study period
10. cost-effectiveness of the intervention at 6 months post-randomisation
Overall trial start date
02/02/2013
Overall trial end date
31/01/2015
Reason abandoned
Eligibility
Participant inclusion criteria
1. Patients requiring mechanical ventilation within 72 hours of admission to intensive care.
2. Male & Female ; Lower Age Limit 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 142; UK Sample Size: 142; Description: Intensive Care Patients
Participant exclusion criteria
1. Age less than 18 years
2. Patient known to be pregnant
3. Known allergy to statin drugs
4. CK > 10 times upper limit of normal range
5. Alanine aminotransferase (ALT) >8 times the upper limit of normal range
6. Patients currently receiving ongoing and sustained treatment with any of the following; itraconazole, ketoconazole, HIV protease inhibitors, nefazodone, cyclosporine, amiodarone, verapamil or diltiazem
7. Uncomplicated elective surgery
8. Patient expected to be discharged within 48 hours of admission
9. Patients with severe renal impairment (estimated creatinine clearance less than 30ml/minute) not receiving renal replacement therapy
10. Severe liver disease
11. Current or recent treatment (within 2 weeks) with statins
12. Physician decision that a statin is required for proven indication
13. Contraindication to enteral drug administration, e.g. patients with mechanical bowel obstruction. Patients with high gastric aspirates due to an ileus are not excluded.
14. Known participation in investigational medicinal product (IMP) trials within 30 days
15. Consent declined
16. Treatment withdrawal likely within 48 hours
17. Non-English speaking patients or those who do not adequately understand verbal or written information
Recruitment start date
02/02/2013
Recruitment end date
31/01/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
West Hertfordshire Hospitals NHS Trust
Watford
WD18 0HB
United Kingdom
Sponsor information
Organisation
West Hertfordshire Hospitals NHS Trust (UK)
Sponsor details
60 Vicarage Road
Watford
WD18 0HB
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
NIHR (UK) - Research for Patient Benefit (RfPB); Grant Codes: PB-PG-0211-24123
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/25982544