Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC)

Overview

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

Full Title of Study: “Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: June 30, 2019

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.

Interventions

  • Drug: Ondansetron 8mg
    • Ondansetron 8 MG prepared in a 100 mL normal saline min-bag
  • Drug: Haloperidol 0.05mg/kg
    • Haloperidol 0.05 mg/kg prepared in a 100 mL normal saline min-bag
  • Drug: Haloperidol 0.1mg/kg
    • Haloperidol 0.1 mg/kg prepared in a 100 mL normal saline min-bag

Arms, Groups and Cohorts

  • Active Comparator: Ondansetron 8mg
    • 8mg Ondansetron prepared in a 100mL normal saline mini-bag
  • Experimental: Haloperidol 0.05mg/kg
    • 0.05mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag
  • Experimental: Haloperidol 0.1mg/kg
    • 0.1mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 100 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Queen’s University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Dr. Marco L.A. Sivilotti, Principal Investigator – Queen’s University
  • Overall Official(s)
    • Marco LA Sivilotti, MD, MSc, Principal Investigator, Dept. of Emergency Medicine, Queen’s University

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.