Olanzapine for Acute Headaches

• Sponsor: HealthPartners Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT03066622
• Collaborator: (none)
• Enrollment: 122
• Location: 1
• Arms: 2
• Actual Duration (Months): 22.6
• Patients Per Site Per Month: 5.4

Study Details

Study Description

Brief Summary

This trial is a prospective, randomized, feasibility trial with the primary aim of comparing how well oral rapidly dissolving olanzapine controls primary headache pain when compared to the current treatment strategies used in emergency departments which often require intravenous or intramuscular medications.

Condition or Disease	Intervention/Treatment	Phase
Headache	Drug: Standard of Care as per attending physician; Drug: 5mg rapidly dissolving olanzapine	Phase 4

Detailed Description

Primary Question:

Does oral rapidly dissolving olanzapine provide efficacious analgesia in patients with acute headache of non-organic origin (primary headache) who come to the ED for abortive therapy when compared to current standard of care?

Secondary Aim:

Additionally, the study will aim to see if oral rapidly dissolving olanzapine decreases 1) duration of ED length of stay and 2) need for IV access when compared to the current standard of care.

This is a prospective, randomized, convenience sample, feasibility trial to test for non-inferiority of oral rapidly dissolving olanzapine versus current emergency department standard of care in providing symptomatic relief to patients presenting with primary headache.

Study Design

• Study Type: Interventional
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a prospective, randomized, convenience sample, feasibility trial to test for non-inferiority of oral rapidly dissolving olanzapine versus current emergency department standard of care in providing symptomatic relief to patients presenting with primary headache.This is a prospective, randomized, convenience sample, feasibility trial to test for non-inferiority of oral rapidly dissolving olanzapine versus current emergency department standard of care in providing symptomatic relief to patients presenting with primary headache.
• Masking: None (Open Label)
• Masking Description: Open label, not blinded, randomized 2-arm trial
• Primary Purpose: Treatment
• Official Title: Oral Rapidly Dissolving Olanzapine for Acute Primary Headache in the Emergency Department Setting: A Feasibility Trial
• Actual Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: May 17, 2018
• Actual Study Completion Date: May 20, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard of Care IV Morphine or any medication per attending decision	Drug: Standard of Care as per attending physician; Patients are randomized to standard of care medication (as determined by attending physician); Other Names: standard of care
Experimental: Olanzapine oral rapidly dissolving olanzapine (Zydis) 5 mg for analgesia in acute primary headaches.	Drug: 5mg rapidly dissolving olanzapine; 5mg rapidly dissolving olanzapine; Other Names: Zydis

Outcome Measures

Primary Outcome Measures

1. Change in Pain Scores Based on Patient Questionnaire [baseline, 30, 60, and 90 minutes post drug administration]

   Change in patient reported pain score from baseline using the Numeric Pain Rating Scale (PNRS) Minimum score = 0 Maximum score = 10 Lower score indicates lower pain level, with zero indicating no pain and 10 indicating the worst pain imaginable.

Secondary Outcome Measures

1. Comparison of Duration of ED Length of Stay [Length of Emergency Department stay (Time Frame: up to 12 hours)]

   The total time the patient spent in the ED after initially being seen by the physician

2. Number of Participants That Receive Peripheral Intravenous Catheterization [Length of Emergency Department stay (Time Frame: up to 12 hours)]

   Determining if patients randomized to rapidly dissolving Olanzapine eventually require IV access, defined as A successful cannulation (blood return or ability to infuse intravenous fluid without infiltration) on initial percutaneous needle puncture

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Adult patient between 18-65 years of age presenting to the emergency department with acute primary headache

2. Patient approved for inclusion by primary attending physician in the emergency department

Exclusion Criteria:

1. Age < 18 or > 65

2. Pregnancy

3. Known allergy to olanzapine

4. Known QT prolongation or underlying condition that places patient at risk for QT prolongation

5. Inability to give written consent (intoxication, altered mental status)

6. Headache of organic origin (trauma, infection, previous recent head or neck surgery)

7. Patient already prescribed daily olanzapine on an outpatient basis

8. Patient has been administered olanzapine within the past 24 hours

9. Language barrier

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Regions Hospital	Saint Paul	Minnesota	United States	55101

Sponsors and Collaborators

• HealthPartners Institute

Investigators

• Principal Investigator: Bradley Hernandez, MD, HealthPartners Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 11, 2016

More Information

Publications

None provided.

• Responsible Party: HealthPartners Institute
• ClinicalTrials.gov Identifier: NCT03066622
• Other Study ID Numbers: 16-420
• First Posted: Feb 28, 2017
• Last Update Posted: Jan 12, 2022
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Headache; Olanzapine

Study Results

Participant Flow

Arm/Group Title	Standard of Care	Olanzapine
Arm/Group Description	Standard of Care medication for treatment of headache as per attending physician: Patients are randomized to standard of care medication (as determined by attending physician)	oral rapidly dissolving olanzapine (Zydis) 5 mg for analgesia in acute primary headaches. 5mg rapidly dissolving olanzapine: 5mg rapidly dissolving olanzapine
Period Title: Overall Study
STARTED	61	61
COMPLETED	35	35
NOT COMPLETED	26	26

Baseline Characteristics

Arm/Group Title	Standard of Care	Olanzapine	Total
Arm/Group Description	Standard of Care medication for treatment of headache as per attending physician: Patients are randomized to standard of care medication (as determined by attending physician)	oral rapidly dissolving olanzapine (Zydis) 5 mg for analgesia in acute primary headaches. 5mg rapidly dissolving olanzapine: 5mg rapidly dissolving olanzapine	Total of all reporting groups
Overall Participants	60	59	119
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.3 (11.2)	34.2 (10.5)	34.2 (10.8)
Sex: Female, Male (Count of Participants)
Female	47 78.3%	42 71.2%	89 74.8%
Male	13 21.7%	17 28.8%	30 25.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 5%	6 10.2%	9 7.6%
Not Hispanic or Latino	57 95%	53 89.8%	110 92.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.7%	1 0.8%
Asian	2 3.3%	2 3.4%	4 3.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	27 45%	22 37.3%	49 41.2%
White	29 48.3%	28 47.5%	57 47.9%
More than one race	2 3.3%	6 10.2%	8 6.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	60 100%	59 100%	119 100%

Outcome Measures

1. Primary Outcome

Title	Change in Pain Scores Based on Patient Questionnaire
Description	Change in patient reported pain score from baseline using the Numeric Pain Rating Scale (PNRS) Minimum score = 0 Maximum score = 10 Lower score indicates lower pain level, with zero indicating no pain and 10 indicating the worst pain imaginable.
Time Frame	baseline, 30, 60, and 90 minutes post drug administration

Outcome Measure Data

Analysis Population Description

Not all participants were assessed at each time point due to some being discharged from the Emergency Department prior to study data collection time points.

Arm/Group Title	Standard of Care	Olanzapine
Arm/Group Description	Standard of Care medication for treatment of headache as per attending physician: Patients are randomized to standard of care medication (as determined by attending physician)	oral rapidly dissolving olanzapine (Zydis) 5 mg for analgesia in acute primary headaches. 5mg rapidly dissolving olanzapine: 5mg rapidly dissolving olanzapine
Measure Participants	58	56
Pain at 30 minutes	-2.95 (2.5)	-1.79 (1.83)
Pain at 60 minutes	-4.49 (2.95)	-2.65 (2.36)
Pain at 90 minutes	-4.68 (2.64)	-3.88 (2.79)

2. Secondary Outcome

Title	Comparison of Duration of ED Length of Stay
Description	The total time the patient spent in the ED after initially being seen by the physician
Time Frame	Length of Emergency Department stay (Time Frame: up to 12 hours)

Outcome Measure Data

Analysis Population Description

Data was only available for 60 subjects in the standard of care arm and 58 subjects in the olanzapine arm.

Arm/Group Title	Standard of Care	Olanzapine
Arm/Group Description	Standard of Care medication for treatment of headache as per attending physician: Patients are randomized to standard of care medication (as determined by attending physician)	oral rapidly dissolving olanzapine (Zydis) 5 mg for analgesia in acute primary headaches. 5mg rapidly dissolving olanzapine: 5mg rapidly dissolving olanzapine
Measure Participants	60	58
Mean (Standard Deviation) [Minutes]	179.57 (83.67)	180.28 (78.60)

3. Secondary Outcome

Title	Number of Participants That Receive Peripheral Intravenous Catheterization
Description	Determining if patients randomized to rapidly dissolving Olanzapine eventually require IV access, defined as A successful cannulation (blood return or ability to infuse intravenous fluid without infiltration) on initial percutaneous needle puncture
Time Frame	Length of Emergency Department stay (Time Frame: up to 12 hours)

Outcome Measure Data

Analysis Population Description

Subjects consenting to participate in the study through time of ED discharge with complete data.

Arm/Group Title	Standard of Care	Olanzapine
Arm/Group Description	Standard of Care medication for treatment of headache as per attending physician: Patients are randomized to standard of care medication (as determined by attending physician)	oral rapidly dissolving olanzapine (Zydis) 5 mg for analgesia in acute primary headaches. 5mg rapidly dissolving olanzapine: 5mg rapidly dissolving olanzapine
Measure Participants	60	58
Count of Participants [Participants]	55 91.7%	28 47.5%

Adverse Events

Time Frame	Adverse event data were collected until completion of the 48 hour follow-up phone call (24-72 hours following enrollment).
Arm/Group Title	Standard of Care		Olanzapine
Arm/Group Description	Standard of Care medication for treatment of headache as per attending physician: Patients are randomized to standard of care medication (as determined by attending physician)		oral rapidly dissolving olanzapine (Zydis) 5 mg for analgesia in acute primary headaches. 5mg rapidly dissolving olanzapine: 5mg rapidly dissolving olanzapine
All Cause Mortality
	Standard of Care		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/59 (0%)
Serious Adverse Events
	Standard of Care		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/59 (0%)
Other (Not Including Serious) Adverse Events
	Standard of Care		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/60 (20%)		11/59 (18.6%)
Ear and labyrinth disorders
Ringing in ears	0/60 (0%)	0	1/59 (1.7%)	1
Gastrointestinal disorders
Nausea	2/60 (3.3%)	2	1/59 (1.7%)	1
General disorders
Dizziness, lightheadedness	4/60 (6.7%)	4	2/59 (3.4%)	2
Drowsiness	2/60 (3.3%)	2	6/59 (10.2%)	6
Jittery feeling	2/60 (3.3%)	2	1/59 (1.7%)	1
Injury, poisoning and procedural complications
Burning sensation at IV site	2/60 (3.3%)	2	0/59 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.