Cannabis Use Disorder
Conditions
Keywords
cannabis, haloperidol, ondansetron, hyperemesis, cyclic vomiting syndrome
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.
Interventions
DRUGOndansetron 8mg
Ondansetron 8 MG prepared in a 100 mL normal saline min-bag
DRUGHaloperidol 0.05mg/kg
Haloperidol 0.05 mg/kg prepared in a 100 mL normal saline min-bag
DRUGHaloperidol 0.1mg/kg
Haloperidol 0.1 mg/kg prepared in a 100 mL normal saline min-bag
Sponsors
Dr. Marco L.A. Sivilotti
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Change in pain | 1, 2, 24 and 48 hours | Changes in abdominal pain score at 1, 2, 24 and 48 hours vs. baseline |
| 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) |
| Rescue anti-emetics in ED | at discharge from Emergency Department or 12 hours whichever comes first | Given rescue anti-emetics prior to discharge |
Countries
Canada
Outcome results
None listed