Back to resultsHaloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC) (HaVOC)
Primary Purpose
Cannabis Use Disorder
Status
Completed
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Ondansetron 8mg
Haloperidol 0.05mg/kg
Haloperidol 0.1mg/kg
Sponsored by
About this trial
This is an interventional treatment trial for Cannabis Use Disorder focused on measuring cannabis, haloperidol, ondansetron, hyperemesis, cyclic vomiting syndrome
Eligibility Criteria
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
Sites / Locations
- Hotel Dieu Hospital
- Kingston General Hospital
- Queen's University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
Ondansetron 8mg
Haloperidol 0.05mg/kg
Haloperidol 0.1mg/kg
Arm Description
8mg Ondansetron prepared in a 100mL normal saline mini-bag
0.05mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag
0.1mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Change in pain
Changes in abdominal pain score at 1, 2, 24 and 48 hours vs. baseline
Change in nausea
Changes in nausea score at 1, 2, 24 and 48 hours vs. baseline
Treatment success
Treatment success = both abdominal pain and nausea score < 2 at 2, 24 and 48 hours
Oral intake
Cumulative oral intake from t=0 to 2 hours (in mL)
Emesis volume
Cumulative emesis from t=0 to 2 hours (in mL)
Urine output
Cumulative urine output (in mL)
Discharge ready at 2 hours
Deemed discharge-ready at 2 hours in the opinion of the treating physician
Rescue anti-emetics in ED
Given rescue anti-emetics prior to discharge
Time to discharge from ED
Time interval to discharge-ready from t=0 (min)
Subject preferred arm
Subject preference of high- vs low-dose haloperidol, and of haloperidol vs ondansetron (-10, 10)
Return to ED
Unscheduled return visits to ED within 7 days (count)
ED consult
Consulted to admitting service
Prolonged ED Length of stay
Outcome 10 "Time to Discharge from ED" > 12 hours (binary yes/no)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03056482
Brief Title
Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC)
Acronym
HaVOC
Official Title
Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
May 21, 2017 (Actual)
Primary Completion Date
June 30, 2019 (Actual)
Study Completion Date
July 7, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Queen's University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cannabis Use Disorder
Keywords
cannabis, haloperidol, ondansetron, hyperemesis, cyclic vomiting syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Participants will be allocated to an intervention via a sealed, opaque envelope system to be opened by an unblinded nurse not otherwise involved in patient care or research procedures will prepare the intervention. The Attending physician, Research personnel and Investigator(s) will all remain blinded to the allocation.
Allocation
Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ondansetron 8mg
Arm Type
Active Comparator
Arm Description
8mg Ondansetron prepared in a 100mL normal saline mini-bag
Arm Title
Haloperidol 0.05mg/kg
Arm Type
Experimental
Arm Description
0.05mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag
Arm Title
Haloperidol 0.1mg/kg
Arm Type
Experimental
Arm Description
0.1mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag
Intervention Type
Drug
Intervention Name(s)
Ondansetron 8mg
Other Intervention Name(s)
Zofran
Intervention Description
Ondansetron 8 MG prepared in a 100 mL normal saline min-bag
Intervention Type
Drug
Intervention Name(s)
Haloperidol 0.05mg/kg
Other Intervention Name(s)
Haldol
Intervention Description
Haloperidol 0.05 mg/kg prepared in a 100 mL normal saline min-bag
Intervention Type
Drug
Intervention Name(s)
Haloperidol 0.1mg/kg
Other Intervention Name(s)
Haldol
Intervention Description
Haloperidol 0.1 mg/kg prepared in a 100 mL normal saline min-bag
Primary Outcome Measure Information:
Title
Change in pain and nausea
Description
Difference between arithmetic mean of Pain Score and Nausea Score (each on a 10-cm VAS) at 2 hours versus at baseline
Time Frame
2 hours
Secondary Outcome Measure Information:
Title
Change in pain
Description
Changes in abdominal pain score at 1, 2, 24 and 48 hours vs. baseline
Time Frame
1, 2, 24 and 48 hours
Title
Change in nausea
Description
Changes in nausea score at 1, 2, 24 and 48 hours vs. baseline
Time Frame
1, 2, 24 and 48 hours
Title
Treatment success
Description
Treatment success = both abdominal pain and nausea score < 2 at 2, 24 and 48 hours
Time Frame
2, 24 and 48 hours
Title
Oral intake
Description
Cumulative oral intake from t=0 to 2 hours (in mL)
Time Frame
2 hours
Title
Emesis volume
Description
Cumulative emesis from t=0 to 2 hours (in mL)
Time Frame
2 hours
Title
Urine output
Description
Cumulative urine output (in mL)
Time Frame
2 hours
Title
Discharge ready at 2 hours
Description
Deemed discharge-ready at 2 hours in the opinion of the treating physician
Time Frame
2 hours
Title
Rescue anti-emetics in ED
Description
Given rescue anti-emetics prior to discharge
Time Frame
at discharge from Emergency Department or 12 hours whichever comes first
Title
Time to discharge from ED
Description
Time interval to discharge-ready from t=0 (min)
Time Frame
at discharge from Emergency Department or 12 hours whichever comes first
Title
Subject preferred arm
Description
Subject preference of high- vs low-dose haloperidol, and of haloperidol vs ondansetron (-10, 10)
Time Frame
2 hours
Title
Return to ED
Description
Unscheduled return visits to ED within 7 days (count)
Time Frame
7 days
Title
ED consult
Description
Consulted to admitting service
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
Title
Prolonged ED Length of stay
Description
Outcome 10 "Time to Discharge from ED" > 12 hours (binary yes/no)
Time Frame
at discharge from Emergency Department or 12 hours whichever comes first
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marco LA Sivilotti, MD, MSc
Organizational Affiliation
Dept. of Emergency Medicine, Queen's University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hotel Dieu Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Facility Name
Kingston General Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Facility Name
Queen's University
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 3N6
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33160719
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.
Results Reference
derived
Learn more about this trial
Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC)
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