Methylphenidate, rivastigmine or haloperidol in hypoactive delirious intensive care patients: a single centre, randomized, mono-blind pilot trial

Delirium is characterized as: (1) Disturbance of consciousness (i.e., reduced
clarity of awareness of the environment) with reduced ability to focus,
sustain, or shift attention. (2) A change in cognition or the development of a
perceptual disturbance that is not better accounted for by a preexisting,
established, or evolving dementia. (3) The disturbance develops over a short
period of time (usually hours to days) and tends to fluctuate during the course
of the day. (4) There is evidence from the history, physical examination, or
laboratory findings that the disturbance is caused by the direct physiological
consequences of a general medical condition. Delirium can be classified into
three different subtypes: hyperactive, hypoactive and mixed type.
Delirium is frequent among ICU patients. ICU-delirium is not only associated
with stress and discomfort of the patient and their relatives, but also with a
worse prognosis. ICU-delirium is also associated with higher ICU and total
hospital costs. According to international guidelines, the treatment severe
aggitation in delirium is haloperidol. This trial will possibly identify new
treatments for delirium.

The purpose of this pilot-trial is the feasibility of a large randomized,
placebo controlled, dubbleblind clinical trial to investigate the use of
methylfenidate, rivastigmine or haloperidol in hypoactive ICU-delirium.
Secondary we will try to compare the outcomes (duration of delirium, severity
of delirium, length of ICU/hospital stay en side effects) between the different
interventions.

single centre, randomized, placebo-controlled, mono-blind pilot trial

Participants of this study will be randomised between for intervention groups:
- Methylphenidate 5 mg. 2 dd 1, oral, increased every day with 10 mg. until
negative CAM(-ICU) or side-effects. Maximum dosage 30 mg./day
- Rivastigmine 1,5 mg. 2 dd 1, oral, increased every third day with 3 mg. until
negative CAM(-ICU) or side-effects. Maximum dosage 12 mg./day
- Haloperidol 2,5 mg. 2 dd 1, oral. (if patient is 69 years or younger)
Haloperidol 1 mg. 2 dd 1, oral (if patient is 70 years or older)
- No intervention

Burden:
The participants will be screened twice a day by the investigator, using the
CAM-ICU (duration: circa 5 minutes). This is a questionnaire and not an
invasive method.
Risks
Rivastigmine and methylphenidate are not registered for the treatment of
delirium, both drugs however are frequently used and extensively tested.
Participants receiving either methylphenidate, rivastigmine or no intervention
will be deprived of the treatment as recommended by international guidelines
(haloperidol). In current practice however haloperidol is only given in case of
severe agitation, and especially hypoactive delirious patients will receive no
therapy at all.