Clinical Trial: Treatment of Hypoactive Delirium and Outcome Measures

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Randomized Double-Blind Clinical Trial to Compare Haloperidol and Non-Pharmacologic Treatment Versus Non-Pharmacologic Treatment and Placebo, in Elderly Hospitalized Patients With Background

Delirium is a cognitive disorder that affects attention and other mental functions. It has an acute onset (in hours or days), a fluctuating course and has various conditioning factors such as diseases or withdrawal or intoxication syndromes.

Delirium is a syndrome with multifactorial origin, it commonly presents in elderly patients, with a prevalence of 20%. Delirium develops when basal vulnerability interacts with precipitating factors.

Delirium has three types according to its psychomotor presentation, hyperactive (agitated), hypoactive (tranquil) or mixed. Delirium has serious outcomes, such as prolonged hospitalization (1), cognitive decline and dementia (2,3,4,), posttraumatic stress disorder (5) and a higher mortality (1).

A neurotransmitter imbalance between acetylcholine and dopamine explains delirium symptoms. A dopamine excess has various consequences: hallucinations that are present in 51 %, and delusions, present in up to 43% in hypoactive delirium. These symptoms produce acute stress in patients and caregivers. It is reported that 53.5% of patients recalled the episode of delirium and from these, 55% of them recalled it associated to hallucinations and 95% of them to delusions. Family recalled the event as stressful in 66%, nurses in 65% of those who did not have hallucinations and in 88% of those who had (6).

Hallucinations and delusions are risk factors for the development of posttraumatic stress disorder, which occurs in up 22% of patients.

Dopamine increase has been associated to apoptosis for its neurotoxic effects. Inflammation has a role in delirium. A study demonstrated that cortisol, Interleuki
Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Current Primary Outcome: Change in delirium severity [ Time Frame: Participants will be followed at an expected average of nine days ]

Reduction of 50% from the basal DOSS score


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Necessity of additional open label haloperidol doses to control delirium symptoms [ Time Frame: Participants will be followed at an expected average of nine days ]

    In case the patient develops a hyperactive state will receive haloperidol in an open label dose, 1 mg that could be repeated every 4 hours in case the agitation persists, for a maximum daily dose of 6 mg. In this way, the dose will never exceed the recommended 10 mg dose per day.

    If the patient persists with a hypoactive state (absence of improvement on the DOSS score), we will increase the dose to 2.5 mg or half a tablet (of haloperidol or placebo q.d.) or 3.75 mg,three quarters of a tablet ( of haloperidol or placebo q.d.)

  • Delirium duration [ Time Frame: Participants will be followed at an expected average of nine days ]
    Using the DOSS basal score and the CAM
  • Perceived stress [ Time Frame: At 24 hours after delirium remission ]
    in patients, health staff and caregivers of both groups using the delirium experience questionnaire
  • Posttraumatic stress disorder [ Time Frame: At 6 months after delirium remission ]
    In patients of both groups using the posttraumatic stress disorder section of the Mini International Neuropsychiatry Interview
  • Cognitive impairment as assessed by Montreal Cognitive Assessment (MoCA) <24 points [ Time Frame: At 6 months after delirium remission ]
    Number of patients with <24 points in the Montreal Cognitive Assessment at 6 months after delirium remission, as compared with the number of patients with scoring >3.5 points in the Informant Questionnaire on Cognitive Decline in the Elderly, as an estimate of the baseline (pre-delirium) state
  • Cerebral blood flow as assessed by transcranial Doppler [ Time Frame: At baseline and after 24 h of delirium remission ]
    in patients of both groups using a cerebral ultrasound
  • Side effects associated with either intervention [ Time Frame: Participants will be followed at an expected average of nine days ]
    We will list all adverse reactions associated with haloperidol (extra pyramidal effects, arrhythmias, hypersensitivity to the drug or corrected QT interval prolongation), the medication will be stopped in case of the appearance of an life-threatening reaction. We will consider this case when a patient needs ventilator support, use of cardiac amines, hemodialysis or the use of the Intensive Care Unit. These conditions will require opening the masking and exit the patient from the study.


Original Secondary Outcome: Same as current

Information By: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Dates:
Date Received: November 7, 2014
Date Started: January 2016
Date Completion: December 2018
Last Updated: April 20, 2017
Last Verified: January 2016