Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC)

Verified February 2017 by Queen’s University

Sponsor:

Information provided by (Responsible Party):

Dr. Marco L.A. Sivilotti, Queen’s University

ClinicalTrials.gov Identifier:

NCT03056482

First received: January 23, 2017

Last updated: February 14, 2017

Last verified: February 2017

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

Cannabis Use Disorder	Drug: Ondansetron 8mg Drug: Haloperidol 0.05mg/kg Drug: Haloperidol 0.1mg/kg	Phase 4

Cannabis Use Disorder

Drug: Ondansetron 8mg
Drug: Haloperidol 0.05mg/kg
Drug: Haloperidol 0.1mg/kg

Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment 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. Masking: Participant, Care Provider, Investigator, Outcomes 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. Primary Purpose: Treatment
Official Title:	Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized Controlled Trial

Study Type:

Interventional

Study Design:

Allocation: Randomized
Intervention Model: Crossover Assignment
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.

Masking: Participant, Care Provider, Investigator, Outcomes 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.

Primary Purpose: Treatment

Official Title:

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

Primary Outcome Measures:

Secondary Outcome 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)

Estimated Enrollment:	80
Anticipated Study Start Date:	April 3, 2017
Estimated Study Completion Date:	July 1, 2019
Estimated Primary Completion Date:	April 1, 2019 (Final data collection date for primary outcome measure)

Active Comparator: Ondansetron 8mg 8mg Ondansetron prepared in a 100mL normal saline mini-bag	Drug: Ondansetron 8mg Ondansetron 8 MG prepared in a 100 mL normal saline min-bag Other Name: Zofran
Experimental: Haloperidol 0.05mg/kg 0.05mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag	Drug: Haloperidol 0.05mg/kg Haloperidol 0.05 mg/kg prepared in a 100 mL normal saline min-bag Other Name: Haldol
Experimental: Haloperidol 0.1mg/kg 0.1mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag	Drug: Haloperidol 0.1mg/kg Haloperidol 0.1 mg/kg prepared in a 100 mL normal saline min-bag Other Name: Haldol

Active Comparator: Ondansetron 8mg

8mg Ondansetron prepared in a 100mL normal saline mini-bag

Drug: Ondansetron 8mg

Ondansetron 8 MG prepared in a 100 mL normal saline min-bag

Other Name: Zofran

Experimental: Haloperidol 0.05mg/kg

0.05mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag

Drug: Haloperidol 0.05mg/kg

Haloperidol 0.05 mg/kg prepared in a 100 mL normal saline min-bag

Other Name: Haldol

Experimental: Haloperidol 0.1mg/kg

0.1mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag

Drug: Haloperidol 0.1mg/kg

Haloperidol 0.1 mg/kg prepared in a 100 mL normal saline min-bag

Other Name: Haldol

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.

Ages Eligible for Study:	18 Years to 100 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03056482

Hotel Dieu Hospital
Kingston, Ontario, Canada, K7L 2V7
Kingston General Hospital
Kingston, Ontario, Canada, K7L 2V7
Queen’s University
Kingston, Ontario, Canada, K7L 3N6

Queen’s University

Principal Investigator:	Marco LA Sivilotti, MD, MSc	Dept. of Emergency Medicine, Queen’s University

Responsible Party:	Dr. Marco L.A. Sivilotti, Principal Investigator, Queen’s University
ClinicalTrials.gov Identifier:	NCT03056482 History of Changes
Other Study ID Numbers:	EMED-251-17
Study First Received:	January 23, 2017
Last Updated:	February 14, 2017
Individual Participant Data
Plan to Share IPD:	No

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No
Product Manufactured in and Exported from the U.S.:		No

Keywords provided by Queen’s University:

cannabis haloperidol ondansetron hyperemesis cyclic vomiting syndrome

Additional relevant MeSH terms:

Marijuana Abuse Hyperemesis Gravidarum Substance-Related Disorders Chemically-Induced Disorders Mental Disorders Morning Sickness Pregnancy Complications Vomiting Signs and Symptoms, Digestive Signs and Symptoms Ondansetron Haloperidol Haloperidol decanoate Antiemetics Autonomic Agents	Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Antipruritics Dermatologic Agents Serotonin Antagonists Serotonin Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Antipsychotic Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs Anti-Anxiety Agents Dopamine Antagonists

ClinicalTrials.gov processed this record on February 17, 2017

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