Clinical trial NCT03056482: Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC)
Official title: Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cannabis Use Disorder
Keywords: cannabis
haloperidol
ondansetron
hyperemesis
cyclic vomiting syndrome
Lead sponsor: Queen's University
Sponsor class: OTHER
First posted: 2017-02-17
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a double-blinded, randomized, cross-over clinical trial that will allocate subjects in a 1:1:1 fashion into one of three treatment groups: high- or low-dose haloperidol, or ondansetron, with a minimum 7-day washout period between treatments.
Primary purpose: TREATMENT

Brief summary: Cannabis Hyperemesis Syndrome (CHS) has become a well-documented syndrome since 2004 and is expected to increase in prevalence with continuing liberalization of marijuana and recognition of the disease. Regardless of whether the association with heavy cannabis use is recognized, there is well-documented resistance to traditional anti-emetic treatment. Given promising reports of the use of intravenous haloperidol, a randomized controlled trial comparing it to the commonly administered anti-emetic ondansetron will contribute to the management of CHS

Detailed description: This is a double-blinded, randomized, cross-over clinical trial that will enroll approximately 80 subjects from at least four different research sites. Patients who have been diagnosed with CHS and enrolled in our study will act as their own controls upon their return to the ED for a subsequent bout of CHS for up to 3 visits per subject. Each patient will be allocated in a 1:1:1 fashion into one of three treatment groups: high- or low-dose haloperidol, or ondansetron, with a minimum 7-day washout period between treatments. As CHS tends to be a recurrent syndrome (presumably given the continued use of cannabis despite recommendations to taper and abstain), it is expected that most subjects will return at least once again, and a substantial subset of the study population will complete all three treatment visits during the trial.

Eligibility criteria: Inclusion Criteria:

1. Age \> 18 years
2. Self-report of ≥3 episodes of emesis occurring in a cyclic pattern for greater than 1 month in the preceding 2 years
3. Current episode \>2 hours of emesis
4. At least one episode of emesis/forceful retching witnessed (including products of emesis at bedside) or heard by an independent observer (healthcare provider or family/friend) in the emergency department
5. Self-reported frequent (near daily to daily x at least 6 months) use of cannabis by inhalation.
6. Working diagnosis of cannabis hyperemesis syndrome in the opinion of the treating emergency physician

Exclusion Criteria:

1. Chronic, daily use of opioid equivalent to ≥10mg morphine/day
2. Inability to comprehend study consent or instructions
3. Unreliable follow-up/unlikely to return for cross-over
4. Administration of an intravenous antiemetic, anticholinergic or antipsychotic (other than up to 100mg dimenhydrinate) in the previous 24 hours
5. Allergy or intolerance to haloperidol or ondansetron
6. Pregnancy
7. Any other medical or psychiatric condition that in the opinion of the enrolling physician would interfere with participation in the trial
8. Current active participation in an investigational drug trial

Primary outcomes:
measure: Change in pain and nausea
timeFrame: 2 hours
Secondary outcomes:
measure: Change in pain
timeFrame: 1, 2, 24 and 48 hours
measure: Change in nausea
timeFrame: 1, 2, 24 and 48 hours
measure: Treatment success
timeFrame: 2, 24 and 48 hours
measure: Oral intake
timeFrame: 2 hours
measure: Emesis volume
timeFrame: 2 hours
measure: Urine output
timeFrame: 2 hours
measure: Discharge ready at 2 hours
timeFrame: 2 hours
measure: Rescue anti-emetics in ED
timeFrame: at discharge from Emergency Department or 12 hours whichever comes first
measure: Time to discharge from ED
timeFrame: at discharge from Emergency Department or 12 hours whichever comes first
measure: Subject preferred arm
timeFrame: 2 hours
measure: Return to ED
timeFrame: 7 days
measure: ED consult
timeFrame: From time of study intervention until admitting service consulted or subject discharged from Emergency Department, whichever comes first, assessed up to 48 hours
measure: Prolonged ED Length of stay
timeFrame: at discharge from Emergency Department or 12 hours whichever comes first
Other outcomes:
Locations:
city: Kingston
country: Canada
facility: Hotel Dieu Hospital
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Kingston
country: Canada
facility: Queen's University
state: Ontario
Study officials:
affiliation: Dept. of Emergency Medicine, Queen's University
name: Marco LA Sivilotti, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ruberto AJ, Sivilotti MLA, Forrester S, Hall AK, Crawford FM, Day AG. Intravenous Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized, Controlled Trial. Ann Emerg Med. 2021 Jun;77(6):613-619. doi: 10.1016/j.annemergmed.2020.08.021. Epub 2020 Nov 5.