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Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC)

Phase 4
Completed
Conditions
Cannabis Use Disorder
Interventions
Registration Number
NCT03056482
Lead Sponsor
Dr. Marco L.A. Sivilotti
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
33
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Ondansetron 8mgOndansetron 8mg8mg Ondansetron prepared in a 100mL normal saline mini-bag
Haloperidol 0.05mg/kgHaloperidol 0.05mg/kg0.05mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag
Haloperidol 0.1mg/kgHaloperidol 0.1mg/kg0.1mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag
Primary Outcome Measures
NameTimeMethod
Change in pain and nausea2 hours

Difference between arithmetic mean of Pain Score and Nausea Score (each on a 10-cm VAS) at 2 hours versus at baseline

Secondary Outcome Measures
NameTimeMethod
Oral intake2 hours

Cumulative oral intake from t=0 to 2 hours (in mL)

ED consultFrom time of study intervention until admitting service consulted or subject discharged from Emergency Department, whichever comes first, assessed up to 48 hours

Consulted to admitting service

Prolonged ED Length of stayat discharge from Emergency Department or 12 hours whichever comes first

Outcome 10 "Time to Discharge from ED" \> 12 hours (binary yes/no)

Change in pain1, 2, 24 and 48 hours

Changes in abdominal pain score at 1, 2, 24 and 48 hours vs. baseline

Change in nausea1, 2, 24 and 48 hours

Changes in nausea score at 1, 2, 24 and 48 hours vs. baseline

Treatment success2, 24 and 48 hours

Treatment success = both abdominal pain and nausea score \< 2 at 2, 24 and 48 hours

Urine output2 hours

Cumulative urine output (in mL)

Discharge ready at 2 hours2 hours

Deemed discharge-ready at 2 hours in the opinion of the treating physician

Rescue anti-emetics in EDat discharge from Emergency Department or 12 hours whichever comes first

Given rescue anti-emetics prior to discharge

Time to discharge from EDat discharge from Emergency Department or 12 hours whichever comes first

Time interval to discharge-ready from t=0 (min)

Subject preferred arm2 hours

Subject preference of high- vs low-dose haloperidol, and of haloperidol vs ondansetron (-10, 10)

Return to ED7 days

Unscheduled return visits to ED within 7 days (count)

Emesis volume2 hours

Cumulative emesis from t=0 to 2 hours (in mL)

Trial Locations

Locations (3)

Kingston General Hospital

🇨🇦

Kingston, Ontario, Canada

Hotel Dieu Hospital

🇨🇦

Kingston, Ontario, Canada

Queen's University

🇨🇦

Kingston, Ontario, Canada

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