The Effect of Intranasal Vasoconstrictor Medications on Hemodynamic Parameters: A Randomized Double-blind, Placebo-controlled Trial.

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02285634
• Collaborator: (none)
• Enrollment: 68
• Location: 1
• Arms: 4
• Actual Duration (Months): 37.7
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

Nosebleeds (epistaxis) are a frequent cause of emergency department visits, reportedly inciting 1 in 200 visits. They are most common in those less than ten and older than seventy, often occurring in the winter months secondary to dry indoor heating. Epistaxis is associated with elevated blood pressures, but it is controversial whether hypertension is actual a contributing cause.

In non-life-threatening epistaxis, the first step in management is commonly the application of a topical vasoconstrictive medication. In many cases this will lead to cessation of the bleeding or facilitate the exam in those that continue to bleed. Frequently used medications include phenylephrine, oxymetazoline, and lidocaine with epinephrine.

Classic teaching has been to avoid the use of these medications in patients with elevated blood pressures due to concerns of inducing hypertensive crisis. Strict avoidance of topical vasoconstrictors in this patient group with epistaxis severely limits the treatment options for a many patients given the association between the two conditions.

Though universally taught, the actual effect of these agents on blood pressure remains unquantified. Studies investigating the prevention of nose bleeding during nasotracheal intubations suggest that the effect might be minor with little variation between agents.

Clinical question:

What is the effect of commonly used intranasal vasoconstrictors on blood pressure in volunteers without a history of hypertension.

Condition or Disease	Intervention/Treatment	Phase
Epistaxis; Blood Pressure	Drug: Oxymetazoline 0.05%; Drug: Phenylephrine 0.25%; Drug: Lidocaine 1% plus epinephrine 1:100,000; Drug: Bacteriostatic 0.9% NaCL	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of Intranasal Vasoconstrictor Medications on Hemodynamic Parameters: A Randomized Double-blind, Placebo-controlled Trial.
• Actual Study Start Date: Nov 1, 2014
• Actual Primary Completion Date: Dec 22, 2016
• Actual Study Completion Date: Dec 22, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oxymetazoline 0.05% Oxymetazoline 0.05%	Drug: Oxymetazoline 0.05%; sterile gauze soaked in 5 milliliters (mL) of Oxymetazoline 0.05% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.
Experimental: Phenylephrine 0.25% Phenylephrine 0.25%	Drug: Phenylephrine 0.25%; sterile gauze soaked in 5 milliliters (mL) of Phenylephrine 0.25% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.
Experimental: Lidocaine 1% plus epinephrine 1:100,000 Lidocaine 1% plus epinephrine 1:100,000	Drug: Lidocaine 1% plus epinephrine 1:100,000; sterile gauze soaked in 5 milliliters (mL) of Lidocaine 1% plus epinephrine 1:100,000 into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.
Placebo Comparator: Bacteriostatic 0.9% sodium chloride (NaCL) Bacteriostatic 0.9% NaCL	Drug: Bacteriostatic 0.9% NaCL; sterile gauze soaked in 5 milliliters (mL) of Bacteriostatic 0.9% NaCL into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.

Outcome Measures

Primary Outcome Measures

1. Change in Mean Arterial Blood Pressure [baseline, 30 minutes]

   Change in mean arterial blood pressure from the baseline measurement

Secondary Outcome Measures

1. Change in Systolic Blood Pressure [baseline, 30 minutes]

   Change from baseline in systolic blood pressure.

2. Change in Diastolic Blood Pressure [baseline, 30 minutes]

   Change from baseline in diastolic blood pressure.

3. Change in Heart Rate [baseline, 30 minutes]

   Change from baseline in heart rate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Healthy volunteers over the age of eighteen that have been recently dismissed from the Emergency Department at Mayo Clinic Hospital, Saint Marys Campus.

• We will recruit a convenience sample of 100 patients from the Emergency Department who have completed their Emergency Department evaluation and treatment and are being discharged to home with non-painful conditions.

Exclusion Criteria:

• We will exclude persons under the age of eighteen

• Vulnerable populations (pregnant patients and prisoners)

• Those with an allergy to any of the study agents

• Those with acute pain

• Those using antihypertensive or antiarrhythmic agents

• Those with significant cardiopulmonary comorbidities (namely history of arrhythmia, coronary artery disease, hypertension, and heart failure)

• Those with concomitant use of Monoamine oxidase A (MAO) Inhibitors

• Those with a diagnosis of angle closure glaucoma or benign prostatic hyperplasia (BPH)

• Those with a history of cerebrovascular disease

• As well as those with a history of previous nasal surgery or known nasal anatomic abnormalities.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Tobias Kummer, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The Journal of Emergency Medicine

Publications

• Bellew SD, Johnson KL, Nichols MD, Kummer T. Effect of Intranasal Vasoconstrictors on Blood Pressure: A Randomized, Double-Blind, Placebo-Controlled Trial. J Emerg Med. 2018 Oct;55(4):455-464. doi: 10.1016/j.jemermed.2018.07.004. Epub 2018 Sep 6.

• Responsible Party: Tobias Kummer, Assistant Professor of Emergency Medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02285634
• Other Study ID Numbers: 14-006312; UL1TR000135
• First Posted: Nov 7, 2014
• Last Update Posted: Oct 2, 2018
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Epistaxis; Lidocaine; Phenylephrine; Epinephrine; Oxymetazoline

Study Results

Participant Flow

Recruitment Details	Healthy volunteers over the age of eighteen that have been recently dismissed from the Emergency Department at Mayo Clinic Hospital, Saint Marys Campus beginning 11-12-14.
Pre-assignment Detail	None to report

Arm/Group Title	Oxymetazoline 0.05%	Phenylephrine 0.25%	Lidocaine 1% Plus Epinephrine 1:100,000	Bacteriostatic 0.9% Sodium Chloride (NaCL)
Arm/Group Description	Oxymetazoline 0.05% Oxymetazoline 0.05%: sterile gauze soaked in 5 milliliters (mL) of Oxymetazoline 0.05% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Phenylephrine 0.25% Phenylephrine 0.25%: sterile gauze soaked in 5 milliliters (mL) of Phenylephrine 0.25% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Lidocaine 1% plus epinephrine 1:100,000 Lidocaine 1% plus epinephrine 1:100,000: sterile gauze soaked in 5 milliliters (mL) of Lidocaine 1% plus epinephrine 1:100,000 into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Bacteriostatic 0.9% NaCL Bacteriostatic 0.9% sodium chloride (NaCL): sterile gauze soaked in 5 milliliters (mL) of Bacteriostatic 0.9% NaCL into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.
Period Title: Overall Study
STARTED	15	20	15	18
COMPLETED	15	20	11	17
NOT COMPLETED	0	0	4	1

Baseline Characteristics

Arm/Group Title	Oxymetazoline 0.05%	Phenylephrine 0.25%	Lidocaine 1% Plus Epinephrine 1:100,000	Bacteriostatic 0.9% NaCL	Total
Arm/Group Description	Oxymetazoline 0.05% Oxymetazoline 0.05%: sterile gauze soaked in 5 milliliters (mL) of Oxymetazoline 0.05% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Phenylephrine 0.25% Phenylephrine 0.25%: sterile gauze soaked in 5 milliliters (mL) of Phenylephrine 0.25% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Lidocaine 1% plus epinephrine 1:100,000 Lidocaine 1% plus epinephrine 1:100,000: sterile gauze soaked in 5 milliliters (mL) of Lidocaine 1% plus epinephrine 1:100,000 into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Bacteriostatic 0.9% sodium chloride (NaCL) Bacteriostatic 0.9% sodium chloride (NaCL): sterile gauze soaked in 5 milliliters (mL) of Bacteriostatic 0.9% NaCL into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Total of all reporting groups
Overall Participants	15	20	11	17	63
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.5 (15.0)	40.0 (16.8)	38.6 (15.7)	31.2 (10.1)	36.0 (14.4)
Sex: Female, Male (Count of Participants)
Female	11 73.3%	8 40%	2 18.2%	8 47.1%	29 46%
Male	4 26.7%	12 60%	9 81.8%	9 52.9%	34 54%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%	20 100%	11 100%	17 100%	63 100%

Outcome Measures

1. Primary Outcome

Title	Change in Mean Arterial Blood Pressure
Description	Change in mean arterial blood pressure from the baseline measurement
Time Frame	baseline, 30 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxymetazoline 0.05%	Phenylephrine 0.25%	Lidocaine 1% Plus Epinephrine 1:100,000	Bacteriostatic 0.9% NaCL
Arm/Group Description	Oxymetazoline 0.05% Oxymetazoline 0.05%: sterile gauze soaked in 5 milliliters (mL) of Oxymetazoline 0.05% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Phenylephrine 0.25% Phenylephrine 0.25%: sterile gauze soaked in 5 milliliters (mL) of Phenylephrine 0.25% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Lidocaine 1% plus epinephrine 1:100,000 Lidocaine 1% plus epinephrine 1:100,000: sterile gauze soaked in 5 milliliters (mL) of Lidocaine 1% plus epinephrine 1:100,000 into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Bacteriostatic 0.9% sodium chloride (NaCL) Bacteriostatic 0.9% sodium chloride (NaCL): sterile gauze soaked in 5 milliliters (mL) of Bacteriostatic 0.9% NaCL into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.
Measure Participants	15	20	11	17
Mean (Standard Deviation) [mmHg]	5.1 (6.8)	6.4 (5.8)	4.6 (8.0)	6.5 (5.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidocaine 1% Plus Epinephrine 1:100,000, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxymetazoline 0.05%, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.52
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Phenylephrine 0.25%, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Change in Systolic Blood Pressure
Description	Change from baseline in systolic blood pressure.
Time Frame	baseline, 30 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxymetazoline 0.05%	Phenylephrine 0.25%	Lidocaine 1% Plus Epinephrine 1:100,000	Bacteriostatic 0.9% NaCL
Arm/Group Description	Oxymetazoline 0.05% Oxymetazoline 0.05%: sterile gauze soaked in 5 milliliters (mL) of Oxymetazoline 0.05% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Phenylephrine 0.25% Phenylephrine 0.25%: sterile gauze soaked in 5 milliliters (mL) of Phenylephrine 0.25% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Lidocaine 1% plus epinephrine 1:100,000 Lidocaine 1% plus epinephrine 1:100,000: sterile gauze soaked in 5 milliliters (mL) of Lidocaine 1% plus epinephrine 1:100,000 into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Bacteriostatic 0.9% sodium chloride (NaCL) Bacteriostatic 0.9% NaCL: sterile gauze soaked in 5 milliliters (mL) of Bacteriostatic 0.9% sodium chloride (NaCL) into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.
Measure Participants	15	20	11	17
Mean (Standard Deviation) [mmHg]	7.5 (9.8)	8.2 (7.2)	3.5 (6.5)	8.9 (5.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidocaine 1% Plus Epinephrine 1:100,000, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxymetazoline 0.05%, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Phenylephrine 0.25%, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Change in Diastolic Blood Pressure
Description	Change from baseline in diastolic blood pressure.
Time Frame	baseline, 30 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxymetazoline 0.05%	Phenylephrine 0.25%	Lidocaine 1% Plus Epinephrine 1:100,000	Bacteriostatic 0.9% NaCL
Arm/Group Description	Oxymetazoline 0.05% Oxymetazoline 0.05%: sterile gauze soaked in 5 milliliters (mL) of Oxymetazoline 0.05% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Phenylephrine 0.25% Phenylephrine 0.25%: sterile gauze soaked in 5 milliliters (mL) of Phenylephrine 0.25% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Lidocaine 1% plus epinephrine 1:100,000 Lidocaine 1% plus epinephrine 1:100,000: sterile gauze soaked in 5 milliliters (mL) of Lidocaine 1% plus epinephrine 1:100,000 into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Bacteriostatic 0.9% sodium chloride (NaCL) Bacteriostatic 0.9% sodium chloride (NaCL): sterile gauze soaked in 5 milliliters (mL) of Bacteriostatic 0.9% NaCL into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.
Measure Participants	15	20	11	17
Mean (Standard Deviation) [mmHg]	5.7 (7.7)	7.9 (6.8)	6.2 (8.3)	9.3 (6.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidocaine 1% Plus Epinephrine 1:100,000, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxymetazoline 0.05%, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Phenylephrine 0.25%, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Change in Heart Rate
Description	Change from baseline in heart rate.
Time Frame	baseline, 30 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxymetazoline 0.05%	Phenylephrine 0.25%	Lidocaine 1% Plus Epinephrine 1:100,000	Bacteriostatic 0.9% NaCL
Arm/Group Description	Oxymetazoline 0.05% Oxymetazoline 0.05%: sterile gauze soaked in 5 milliliters (mL) of Oxymetazoline 0.05% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Phenylephrine 0.25% Phenylephrine 0.25%: sterile gauze soaked in 5 milliliters (mL) of Phenylephrine 0.25% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Lidocaine 1% plus epinephrine 1:100,000 Lidocaine 1% plus epinephrine 1:100,000: sterile gauze soaked in 5 milliliters (mL) of Lidocaine 1% plus epinephrine 1:100,000 into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.	Bacteriostatic 0.9% sodium chloride (NaCL) Bacteriostatic 0.9% sodium chloride (NaCL): sterile gauze soaked in 5 milliliters (mL) of Bacteriostatic 0.9% NaCL into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.
Measure Participants	15	20	11	17
Mean (Standard Deviation) [beats/min]	2.8 (5.2)	5.2 (6.6)	7.5 (9.7)	6.8 (5.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidocaine 1% Plus Epinephrine 1:100,000, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxymetazoline 0.05%, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Phenylephrine 0.25%, Bacteriostatic 0.9% NaCL
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.47
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Adverse events were collected for the duration of the study protocol. Total observation time was 30 minutes and after completion of the study protocol any adverse effects were recorded.
Arm/Group Title	Oxymetazoline 0.05%		Phenylephrine 0.25%		Lidocaine 1% Plus Epinephrine 1:100,000		Bacteriostatic 0.9% NaCL
Arm/Group Description	Oxymetazoline 0.05% Oxymetazoline 0.05%: sterile gauze soaked in 5 milliliters (mL) of Oxymetazoline 0.05% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.		Phenylephrine 0.25% Phenylephrine 0.25%: sterile gauze soaked in 5 milliliters (mL) of Phenylephrine 0.25% into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.		Lidocaine 1% plus epinephrine 1:100,000 Lidocaine 1% plus epinephrine 1:100,000: sterile gauze soaked in 5 milliliters (mL) of Lidocaine 1% plus epinephrine 1:100,000 into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.		Bacteriostatic 0.9% sodium chloride (NaCL) Bacteriostatic 0.9% sodium chloride (NaCL): sterile gauze soaked in 5 milliliters (mL) of Bacteriostatic 0.9% NaCL into one nostril and placement of a nasal clamp. The nasal clamp and medication will be removed after 15 minutes.
All Cause Mortality
	Oxymetazoline 0.05%		Phenylephrine 0.25%		Lidocaine 1% Plus Epinephrine 1:100,000		Bacteriostatic 0.9% NaCL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/20 (0%)		0/11 (0%)		0/17 (0%)
Serious Adverse Events
	Oxymetazoline 0.05%		Phenylephrine 0.25%		Lidocaine 1% Plus Epinephrine 1:100,000		Bacteriostatic 0.9% NaCL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/20 (0%)		0/11 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Oxymetazoline 0.05%		Phenylephrine 0.25%		Lidocaine 1% Plus Epinephrine 1:100,000		Bacteriostatic 0.9% NaCL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/15 (26.7%)		3/20 (15%)		0/11 (0%)		2/17 (11.8%)
Eye disorders
Eye watering	1/15 (6.7%)	1	0/20 (0%)	0	0/11 (0%)	0	0/17 (0%)	0
General disorders
Nasal Pain	2/15 (13.3%)	2	2/20 (10%)	2	0/11 (0%)	0	0/17 (0%)	0
Diziness	0/15 (0%)	0	1/20 (5%)	1	0/11 (0%)	0	0/17 (0%)	0
Unpleasant aftertaste	1/15 (6.7%)	1	1/20 (5%)	1	0/11 (0%)	0	2/17 (11.8%)	2

Limitations/Caveats

The primary limitation was the small sample size as enrollment was markedly more difficult than anticipated.

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.