Condition category
Mental and Behavioural Disorders
Date applied
26/03/2013
Date assigned
26/03/2013
Last edited
27/08/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

http://www.westhertshospitals.nhs.uk/

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

Publication citations

Additional files

Editorial Notes