Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized Controlled Trial

Conditions
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Cannabis Use Disorder

Intervention / Treatment
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* Drug: Ondansetron 8mg
* Drug: Haloperidol 0.05mg/kg
* Drug: Haloperidol 0.1mg/kg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Self-report of ≥3 episodes of emesis occurring in a cyclic pattern for greater than 1 month in the preceding 2 years Current episode >2 hours of emesis 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 Self-reported frequent (near daily to daily x at least 6 months) use of cannabis by inhalation. Working diagnosis of cannabis hyperemesis syndrome in the opinion of the treating emergency physician Exclusion Criteria: Chronic, daily use of opioid equivalent to ≥10mg morphine/day Inability to comprehend study consent or instructions Unreliable follow-up/unlikely to return for cross-over Administration of an intravenous antiemetic, anticholinergic or antipsychotic (other than up to 100mg dimenhydrinate) in the previous 24 hours Allergy or intolerance to haloperidol or ondansetron Pregnancy Any other medical or psychiatric condition that in the opinion of the enrolling physician would interfere with participation in the trial Current active participation in an investigational drug trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ondansetron 8mg<br>8mg Ondansetron prepared in a 100mL normal saline mini-bag | Drug: Ondansetron 8mg<br>* Ondansetron 8 MG prepared in a 100 mL normal saline min-bag<br>* Other names: Zofran;|
| Experimental: Haloperidol 0.05mg/kg<br>0.05mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag | Drug: Haloperidol 0.05mg/kg<br>* Haloperidol 0.05 mg/kg prepared in a 100 mL normal saline min-bag<br>* Other names: Haldol;|
| Experimental: Haloperidol 0.1mg/kg<br>0.1mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag | Drug: Haloperidol 0.1mg/kg<br>* Haloperidol 0.1 mg/kg prepared in a 100 mL normal saline min-bag<br>* Other names: Haldol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain and nausea | Difference between arithmetic mean of Pain Score and Nausea Score (each on a 10-cm VAS) at 2 hours versus at baseline | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain | Changes in abdominal pain score at 1, 2, 24 and 48 hours vs. baseline | 1, 2, 24 and 48 hours | 
| Change in nausea | Changes in nausea score at 1, 2, 24 and 48 hours vs. baseline | 1, 2, 24 and 48 hours | 
| Treatment success | Treatment success = both abdominal pain and nausea score < 2 at 2, 24 and 48 hours | 2, 24 and 48 hours | 
| Oral intake | Cumulative oral intake from t=0 to 2 hours (in mL) | 2 hours | 
| Emesis volume | Cumulative emesis from t=0 to 2 hours (in mL) | 2 hours | 
| Urine output | Cumulative urine output (in mL) | 2 hours | 
| Discharge ready at 2 hours | Deemed discharge-ready at 2 hours in the opinion of the treating physician | 2 hours | 
| Rescue anti-emetics in ED | Given rescue anti-emetics prior to discharge | at discharge from Emergency Department or 12 hours whichever comes first | 
| Time to discharge from ED | Time interval to discharge-ready from t=0 (min) | at discharge from Emergency Department or 12 hours whichever comes first | 
| Subject preferred arm | Subject preference of high- vs low-dose haloperidol, and of haloperidol vs ondansetron (-10, 10) | 2 hours | 
| Return to ED | Unscheduled return visits to ED within 7 days (count) | 7 days | 
| ED consult | Consulted to admitting service | From time of study intervention until admitting service consulted or subject discharged from Emergency Department, whichever comes first, assessed up to 48 hours | 
| Prolonged ED Length of stay | Outcome 10 Time to Discharge from ED > 12 hours (binary yes/no) | at discharge from Emergency Department or 12 hours whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cannabis, haloperidol, ondansetron, hyperemesis, cyclic vomiting syndrome