The Oslo Study of Clonidine in Elderly Patients With Delirium

Study Overview
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Brief Summary
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Delirium (acute confusional state)is characterized by an acute decline in attention and cognition, and is a common clinical syndrome in elderly patients. The purpose of this randomised, controlled, parallel group pilot trial is to explore superiority of clonidine vs placebo in decreasing delirium in patients diagnosed delirium at the acute geriatric ward. We will also study the feasibility of oral clonidine in a geriatric ward and effects of clonidine upon a variety of outcomes as a means to design a more definite study later.

Official Title
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The Oslo Study of Clonidine in Elderly Patients With Delirium

Conditions
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Delirium

Intervention / Treatment
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* Drug: Clonidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient > 65 years old admitted to the Medical department Delirium or subsyndromal delirium diagnosed within the last 48 hours Signed informed consent from patient or relatives Expected cooperation of the patients for the treatment and follow up Exclusion Criteria: Symptomatic bradycardia, bradycardia due to sick-sinus-syndrome, second- or third- degree AV-block (not treated With pacemaker) or any other reason causing HR <50 bpm at time of inclusion Symptomatic hypotension or orthostatic hypotension, or a systolic BP <120 at the time of inclusion Ischemic stroke within the last 3 months or critical peripheral ischemia Acute coronary syndrome, unstable or severe coronary heart disease (symptoms at minimal physical activity; NYHA 3 and 4) and moderate to severe heart failure (NYHA 3 and 4). A diagnosis of polyneuropathy or pheochromocytoma Renal insufficiency (estimated GFR<30 ml/min according to the MDRD formula). Body weight < 45 kg. Considered as moribund on admission. Not able to take oral medications Current use of tricyclic antidepressants, monoamine reuptake inhibitors or ciclosporin Previously included in this study Adverse reactions to clonidine or excipients (lactose, saccharose) Not speaking or reading Norwegian Any other condition as evaluated by the treating physician Admitted to the ICU

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clonidine<br>Clonidine administered orally: Day 1/loading doses: 75µg every 3rd hour until maximum 4 doses. Day 2-7/maintenance doses: 75µg BID. Duration of treatment is maximum 7 days. | Drug: Clonidine<br> <br> |
| Placebo Comparator: Placebo (sugar pill)<br>Placebo administered orally (identical capsula as for expirimental drug): Day 1/loading doases: 75µg every 3rd hour until maximum 4 doses. Day 2-7/maintenance doses: 75µg BID. Duration of treatment is maximum 7 days. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MDAS (Memorial delirium assessment scale) |  | Participants will be followed for the duration of hospital stay, an expected average of approximately 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-first delirium | We will compare the actively treated group with the placebo group (also with subanalyses for subsyndromal delirium and hypoactive/ hyperactive/ mixed delirium) with respect to: • time to first resolution, monitored by DSM-5 criteria | 2 weeks | 
| Incidence of full-scale delirium | • monitored by DSM-5 criteria | 2 weeks | 
| Severity of delirium | measured by MDAS, OSLA | 2 weeks | 
| Delirium subtype | Measured by MDAS, OSLA | 2 weeks | 
| The use of rescue medication |  | 2 weeks | 
| Length of hospital stay |  | Hospital stay | 
| Patient distress |  | 2 weeks | 
| Side effects of clonidine |  | 4 months | 
| Pharmacokinetic response to clonidine |  | 1 week | 
| Pharmacodynamic response to clonidine |  | 2 weeks | 
| Biomarkers |  | 2 weeks | 
| Institutionalization |  | 4 months | 
| Survival |  | 4 months | 
| Cognitive function/ independence |  | 4 months |