Delirium Clinical Trial
— HaloquetOfficial title:
Randomized Controlled Trial Comparing Haloperidol, Quetiapine and Placebo in the Pharmacological Treatment of Delirium : The Haloquet Trial
Verified date | July 2016 |
Source | Centre hospitalier de l'Université de Montréal (CHUM) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Background:
Delirium is an important problem in critical care. Its prevalence often reaches 75% in
intensive care patients. Its occurrence is associated with numerous complications and
deleterious consequences such as death, longer stay, higher cost, and long-term cognitive
impairment. Delirium treatment entails correcting its underlying causes and usually
initiating a pharmacological intervention with an antipsychotic. Typical antipsychotics,
particularly haloperidol, are commonly used to treat delirium although few placebo-controlled
trials of pharmacological treatments for delirium have been conducted. Furthermore,
appropriate doses for delirium treatment have yet to be established. In critical care, two
pilot studies provided the first randomized, placebo-controlled evidence for the
pharmacologic treatment of ICU delirium. One found that neither haloperidol nor ziprasidone
significantly reduced the incidence or duration of delirium compared with placebo whereas the
other one found that quetiapine added to as-needed haloperidol resulted in faster delirium
resolution.
Objective:
The goal of this study is to determine the effectiveness of antipsychotics in regular dosage
regimen (quetiapine group and haloperidol group) compared to as-needed haloperidol (placebo
group) in the pharmacological treatment of delirium. We will conduct a three-arm randomized
controlled trial to achieve this goal.
Materials and Methods:
During one year, 45 delirious patients from three intensive care units will be recruited and
randomized into one of three groups. Randomization will be performed in blocks of 9 by the
pharmacy department, using a random numbers table.
Patients will be continuously screened for delirium using the Intensive Care Delirium
Screening Checklist (ICDSC) as part of routine care. A positive screening score (≥4) will
warrant confirmation of delirium diagnosis by the treating physician. Treatment will begin
according to randomization group, provided that informed consent has been obtained. Delirium
status will be monitored during the episode using the Nursing Delirium Screening Scale
(Nu-DESC). When the Nu-DESC monitoring will become negative for delirium (total score below
2), the resolution of the episode will be confirmed by the treating physician. A clinical
evaluation by a psychiatrist will be performed within 24-48 hours of each of the two
evaluations made by the treating physician (beginning and end of the delirium episode).
The treating physician will initiate twice-daily treatment at the first of five levels for
each of the three groups: 1) 1 mg of intravenous (IV) haloperidol + oral (PO) placebo, 2) 50
mg of PO quetiapine + IV placebo, or 3) IV + PO placebo. Therapy will be titrated upwards on
a daily basis by increments of 1) 1 mg of IV haloperidol or 2) 50 mg of PO quetiapine, or 3)
IV + PO placebo every 12 hrs, respectively, if the subject received at least two doses of
as-needed haloperidol in the previous 24 hrs. As-needed (PRN) doses of 2 mg of IV haloperidol
q 30 minutes will be available to patients from all three groups and administered by nurses
until symptoms associated with delirium resolve. In case of unsuccessful as-needed treatment,
rescue (STAT) doses of 5 mg of IV haloperidol q 30 minutes will be available to patients from
all three groups and will be administered by nurses if agreement is reached with the treating
physician that the situation indeed calls for it. The treatment level of patients requiring a
STAT dose will immediately be raised to the above level. The treatment will stop when one of
the following occurs: (1) the subject is deemed by the treating physicians, based on their
clinical judgment, to no longer demonstrate signs of delirium and, therefore, to no longer
require scheduled therapy with an antipsychotic agent; (2) 21 days of therapy has elapsed;
(3) ICU discharge occurred; or (4) a life-threatening adverse event potentially attributable
to the study drug occurred that warranted discontinuation of the study drug.
Adverse effects will be closely monitored: extrapyramidal reactions, neuroleptic malignant
syndrome, drowsiness, hypotension, QTc prolongation. The treatment level of patients
presenting a non life-threatening adverse event will immediately be lowered to the level
directly below.
The sample size was calculated for a 2-tailed test with an alpha of .05 and a power of .80.
The primary statistical analysis will involve Cox proportional time to event analysis
comparing the three groups. Secondary analysis will use T-test comparisons for continuous
variables and chi square for proportional analysis.
Status | Completed |
Enrollment | 107 |
Est. completion date | September 2016 |
Est. primary completion date | September 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Patients aged 18 years or older. - Patients with a diagnosis of delirium made by a psychiatrist. Exclusion Criteria: - Patients with active schizophrenia or bipolar disorder. - Patients with Parkinson disease. - Patients with severe liver failure. - Patients with alcohol or sedative/hypnotics dependence. - Patients with QTc interval above 500 msec. - Pregnant patients. |
Country | Name | City | State |
---|---|---|---|
Canada | Centre hospitalier de l'Université de Montréal (CHUM) | Montreal | Quebec |
Lead Sponsor | Collaborator |
---|---|
Centre hospitalier de l'Université de Montréal (CHUM) | Fondation des pompiers du Québec pour les grands brûlés |
Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Time to first resolution of delirium | Confirmed by clinical evaluation of a psychiatrist | 21 days | |
Secondary | Days in delirium during the study | From log | 21 days | |
Secondary | Duration of delirium | From log | 21 days | |
Secondary | Severity of delirium (highest Nu-DESC score, mean episode Nu-DESC score) | Nursing evaluation every 8 hours- shift | 21 days | |
Secondary | ICU and hospital mortality | From the chart | 21 days | |
Secondary | ICU and hospital length of stay | From the chart | 21 days | |
Secondary | Length of mechanical ventilation | From daily clinical évaluation | 21 days | |
Secondary | Time spent deeply sedated (RASS <3) | From chart | 21 days | |
Secondary | Episodes of subject-initiated device removal | From daily clinical évaluation | 21 days | |
Secondary | Use of haloperidol therapy (including total dose in haloperidol equivalents during the study, number of doses, number of days of therapy, use of rescue IV haloperidol) | From long | 21 days | |
Secondary | Average daily and maximum total antipsychotic drug dose in haloperidol equivalents | From long | 21 days | |
Secondary | Duration of study drug administration | From log | 21 days | |
Secondary | Use of benzodiazepines | All benzodiazepines received in lorazepam equivalent | 21 days | |
Secondary | Use of opioids | All opioids received in morphine équivalent | 21 days | |
Secondary | QTc prolongation | From EKG recording | 21 days | |
Secondary | Extrapyramidal symptoms | Daily clinical evaluation | 21 days | |
Secondary | Neuroleptic malignant syndrome | Daily clinical evaluation | 21 days |
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