Cannabis Use DisorderPhase 4HaVOCNCT03056482
Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC)
A Phase 4 study testing Ondansetron 8mg, Haloperidol 0.05mg/kg and Haloperidol 0.1mg/kg in people with Cannabis Use Disorder, run by Dr. Marco L.A. Sivilotti at 3 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Cannabis Use Disorder
- What is being tested?
- Ondansetron 8mg, Haloperidol 0.05mg/kg and Haloperidol 0.1mg/kg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 3 sitesCanada
- Study dates
- 21 May 2017to 7 Jul 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Hotel Dieu Hospital
Kingston, Ontario, K7L 2V7
Kingston General Hospital
Kingston, Ontario, K7L 2V7
Queen's University
Kingston, Ontario, K7L 3N6
About this study
Official title: Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized Controlled Trial
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
Read the 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.
- Conditions
- Cannabis Use Disorder
- Being tested
- Ondansetron 8mg, Haloperidol 0.05mg/kg, Haloperidol 0.1mg/kg
- Keywords
- cannabis, haloperidol, ondansetron, hyperemesis, cyclic vomiting syndrome
- Medical subject headings
- Marijuana Abuse, Hyperemesis Gravidarum, Familial cyclic vomiting syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ondansetron 8mgDrug
Also called Zofran
Ondansetron 8 MG prepared in a 100 mL normal saline min-bag
Haloperidol 0.05mg/kgDrug
Also called Haldol
Haloperidol 0.05 mg/kg prepared in a 100 mL normal saline min-bag
Haloperidol 0.1mg/kgDrug
Also called Haldol
Haloperidol 0.1 mg/kg prepared in a 100 mL normal saline min-bag
| Study group | Role | What they receive |
|---|---|---|
| Ondansetron 8mg | Active comparator | 8mg Ondansetron prepared in a 100mL normal saline mini-bag Receives: Drug: Ondansetron 8mg |
| Haloperidol 0.05mg/kg | Experimental | 0.05mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag Receives: Drug: Haloperidol 0.05mg/kg |
| Haloperidol 0.1mg/kg | Experimental | 0.1mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag Receives: Drug: Haloperidol 0.1mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 hours
Secondary outcomes (13)
Change in pain
Changes in abdominal pain score at 1, 2, 24 and 48 hours vs. baseline
Measured: 1, 2, 24 and 48 hours
Change in nausea
Changes in nausea score at 1, 2, 24 and 48 hours vs. baseline
Measured: 1, 2, 24 and 48 hours
Treatment success
Treatment success = both abdominal pain and nausea score < 2 at 2, 24 and 48 hours
Measured: 2, 24 and 48 hours
Oral intake
Cumulative oral intake from t=0 to 2 hours (in mL)
Measured: 2 hours
Emesis volume
Cumulative emesis from t=0 to 2 hours (in mL)
Measured: 2 hours
Urine output
Cumulative urine output (in mL)
Measured: 2 hours
Discharge ready at 2 hours
Deemed discharge-ready at 2 hours in the opinion of the treating physician
Measured: 2 hours
Rescue anti-emetics in ED
Given rescue anti-emetics prior to discharge
Measured: at discharge from Emergency Department or 12 hours whichever comes first
Time to discharge from ED
Time interval to discharge-ready from t=0 (min)
Measured: at discharge from Emergency Department or 12 hours whichever comes first
Subject preferred arm
Subject preference of high- vs low-dose haloperidol, and of haloperidol vs ondansetron (-10, 10)
Measured: 2 hours
Return to ED
Unscheduled return visits to ED within 7 days (count)
Measured: 7 days
ED consult
Consulted to admitting service
Measured: From time of study intervention until admitting service consulted or subject discharged from Emergency Department, whichever comes first, assessed up to 48 hours
Prolonged ED Length of stay
Outcome 10 "Time to Discharge from ED" > 12 hours (binary yes/no)
Measured: at discharge from Emergency Department or 12 hours whichever comes first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2017
- Study start21 May 2017
- Primary completion30 Jun 2019
- Study completion7 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cannabis Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Marco L.A. Sivilotti
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Marco L.A. Sivilotti, Queen's University
- Investigators
- Marco LA Sivilotti, MD, MSc, Principal investigator, Dept. of Emergency Medicine, Queen's University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03056482
- Sponsor's protocol ID
- EMED-251-17
- Acronym
- HaVOC
- Status last verified
- Apr 2024
- First submitted
- 23 Jan 2017
- Last updated
- 3 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33160719
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03056482
- Acronym / sponsor ID
- HaVOC / EMED-251-17
- Conditions
- Cannabis Use Disorder
- Keywords
- cannabis, haloperidol, ondansetron, hyperemesis, cyclic vomiting syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Dr. Marco L.A. SivilottiUniversity, hospital or other
- Study start
- 21 May 2017 (actual)
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 7 Jul 2019 (actual)
- First posted
- 17 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Ondansetron 8mg | Active comparator | Drug: Ondansetron 8mg8mg Ondansetron prepared in a 100mL normal saline mini-bag |
| Haloperidol 0.05mg/kg | Experimental | Drug: Haloperidol 0.05mg/kg0.05mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag |
| Haloperidol 0.1mg/kg | Experimental | Drug: Haloperidol 0.1mg/kg0.1mg/kg of Haloperidol prepared in a 100mL normal saline mini-bag |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ondansetron 8mgAlso: ZofranOndansetron 8 MG prepared in a 100 mL normal saline min-bag | Drug | Ondansetron 8mg |
| Haloperidol 0.05mg/kgAlso: HaldolHaloperidol 0.05 mg/kg prepared in a 100 mL normal saline min-bag | Drug | Haloperidol 0.05mg/kg |
| Haloperidol 0.1mg/kgAlso: HaldolHaloperidol 0.1 mg/kg prepared in a 100 mL normal saline min-bag | Drug | Haloperidol 0.1mg/kg |
Primary outcome
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
13 secondary outcomes
Change in pain
Time frame: 1, 2, 24 and 48 hours
Change in nausea
Time frame: 1, 2, 24 and 48 hours
Treatment success
Time frame: 2, 24 and 48 hours
Oral intake
Time frame: 2 hours
Emesis volume
Time frame: 2 hours
Urine output
Time frame: 2 hours
Discharge ready at 2 hours
Time frame: 2 hours
Rescue anti-emetics in ED
Time frame: at discharge from Emergency Department or 12 hours whichever comes first
Time to discharge from ED
Time frame: at discharge from Emergency Department or 12 hours whichever comes first
Subject preferred arm
Time frame: 2 hours
Return to ED
Time frame: 7 days
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
Prolonged ED Length of stay
Time frame: at discharge from Emergency Department or 12 hours whichever comes first
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2024.
- Derived from this study: PubMed 33160719Ruberto 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco LA Sivilotti, MD, MSc principal investigator
Dept. of Emergency Medicine, Queen's University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ondansetron 8mg, Haloperidol 0.05mg/kg and Haloperidol 0.1mg/kg in people with Cannabis Use Disorder, run by Dr. Marco L.A. Sivilotti at 3 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in pain and nausea (time frame: 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03056482, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2024.