Background: The Oslo Study of Clonidine in Elderly Patients with Delirium (LUCID) is an RCT investigating the effect of clonidine in medical patients > 65 years with delirium. To assess the dosage regimen and safety measures of this study protocol, we measured the plasma concentrations and hemodynamic effects of clonidine in the first 20 patients.
Methods: Patients were randomised to clonidine (n = 10) or placebo (n = 10). The treatment group was given a loading dose (75μg every 3rd hour up to a maximum of 4 doses) to reach steady state, and further 75μg twice daily until delirium free for 2 days, discharge or a maximum of 7 days. Blood pressure (BP) and heart rate (HR) were measured just before every dose. If the systolic BP was < 100 mmHg or HR < 50 beats per minute the next dose was omitted. Plasma concentrations of clonidine were measured 3 h after each drug intake on day 1, just before intake (day 2 and at steady state day 4-6) and 3 h after intake at steady state (Cmax). Our estimated pre-specified plasma concentration target range was 0.3-0.7μg/L.
Results: 3 h after the first dose of 75μg clonidine, plasma concentration levels rose to median 0.35 (range 0.24-0.40)μg/L. Median trough concentration (C0) at day 2 was 0.70 (0.47-0.96)μg/L. At steady state, median C0 was 0.47 (0.36-0.76)μg/L, rising to Cmax 0.74 (0.56-0.95)μg/L 3 h post dose. A significant haemodynamic change from baseline was only found at a few time-points during the loading doses within the clonidine group. There was however extensive individual BP and HR variation in both the clonidine and placebo groups, and when comparing the change scores (delta values) between the clonidine and the placebo groups, there were no significant differences.
Conclusions: The plasma concentration of clonidine was at the higher end of the estimated therapeutic range. Hemodynamic changes during clonidine treatment were as expected, with trends towards lower blood pressure and heart rate in patients treated with clonidine, but with dose adjustments based on SBP this protocol appears safe.
Trial registration: ClinicalTrials.gov NCT01956604 , 09.25.2013. EudraCT Number: 2013-000815-26, 03.18.2013. Enrolment of first participant: 04.24.2014.
Keywords: Clonidine; Delirium; Pharmacokinetic; RCT.