Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC)

Sponsor

Queen's University (Other)

Overall Status

Completed

CT.gov ID

NCT03056482

Collaborator

(none)

Enrollment

Locations

Arms

25.5

Actual Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Cannabis Use Disorder	Drug: Ondansetron 8mg Drug: Haloperidol 0.05mg/kg Drug: Haloperidol 0.1mg/kg	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

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.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 (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

Actual Study Start Date :

May 21, 2017

Actual Primary Completion Date :

Jun 30, 2019

Actual Study Completion Date :

Jul 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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 Names: Haldol

Arm

Intervention/Treatment

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 Names:

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 Names:

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 Names:

Haldol

Outcome Measures

Primary Outcome Measures

Change in pain and nausea [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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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