Modifying Delirium Using Simvastatin
| ISRCTN | ISRCTN89079989 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN89079989 |
| EudraCT/CTIS number | 2012-003114-13 |
| Secondary identifying numbers | 13988 |
- Submission date
- 26/03/2013
- Registration date
- 26/03/2013
- Last edited
- 17/05/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
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
Contact information
Scientific
60 Vicarage Road
Watford
WD18 0HB
United Kingdom
| valerie.page@whht.nhs.uk |
Study information
| Study design | Randomised double-blind placebo-controlled trial, Design type: Prevention, Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in mechanically ventilated patients at high risk of delirium: a randomised double-blind placebo controlled trial |
| Study acronym | MoDUS |
| Study objectives | 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. |
| Ethics approval(s) | NRES Committee North East - Newcastle & North Tyneside 1, 06/12/2012, ref: 12/NE/0383 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Simvastatin |
| Primary outcome measure | 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 study start date | 02/02/2013 |
| Completion date | 31/01/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 142; UK Sample Size: 142; Description: Intensive Care Patients |
| Key inclusion criteria | 1. Patients requiring mechanical ventilation within 72 hours of admission to intensive care. 2. Male & Female ; Lower Age Limit 18 years |
| Key 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 |
| Date of first enrolment | 02/02/2013 |
| Date of final enrolment | 31/01/2015 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
WD18 0HB
United Kingdom
Sponsor information
Hospital/treatment centre
60 Vicarage Road
Watford
WD18 0HB
England
United Kingdom
| Website | http://www.westhertshospitals.nhs.uk/ |
|---|---|
"ROR" |
https://ror.org/03e4g1593 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 16/05/2015 | Yes | No | |
| Results article | results | 01/09/2017 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
17/05/2018: Publication reference added.
