Comparative Efficacy of Three Preparations of Botox-A in Treating Spasticity

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Completed
• CT.gov ID: NCT00178646
• Collaborator: Allergan (Industry)
• Enrollment: 33
• Locations: 2
• Arms: 3
• Duration (Months): 97.9
• Patients Per Site: 16.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The study seeks to compare the effectiveness of three preparations of BOTOX-A® in treating muscle tightness and spasms in the feet and ankles of people with stroke.

Condition or Disease	Intervention/Treatment	Phase
Stroke; Brain Injuries; Spasticity	Drug: Botox	Phase 4

Detailed Description

Spasticity is one of the most debilitating complications of neurologic conditions, such as stroke, brain injury, spinal cord injury, cerebral palsy, and multiple sclerosis. Although the exact pathophysiology is unknown, it is believed to result from an imbalance of ascending excitatory influences on and descending inhibitory components of the central nervous system. Clinically, spasticity manifests as abnormally increased muscle tone, associated with loss of range of motion, increased muscle stretch reflexes, clonus, weakness, and incoordination. If inadequately treated, spasticity leads to more disability and increase health care costs. Common complications of inadequately treated spasticity include joint and muscle contracture, pain, difficulty with performing activities of daily living and hygiene, and impaired transfers and ambulation.

Acquired brain injuries (ABI), including stroke, traumatic brain injury, and encephalopathy, often lead to long-term impairments, including spasticity. In severe cases, spasticity is difficult and frustrating to treat in this patient population, since the individuals may not tolerate the side effects of conventional therapies because of ABI-related deficits in arousal and cognition. Systemic medications, such as baclofen and tizanidine, are effective in controlling spasticity; however, they may also cause sleepiness and drowsiness, and impair memory and thinking processes---adverse effects that individuals with ABI may not tolerate.

Thus, "local" treatments, such as neurolysis and chemodenervation using botulinum toxin, have become superior treatment options in individuals with ABI, since they are devoid of the usual side effects of systemic medications. They are also effective in controlling spasticity, yet they do not impair arousal and cognition. The medical literature is replete with reports of the efficacy of botulinum toxin-A in the management of spasticity. Thus, the current challenge for clinicians and researchers at this time is to find ways to further enhance the efficacy of botulinum toxin. One way to achieve this is by exploiting certain properties of the toxin. Animal studies and clinical experience have shown that the effects of the drug is dose-dependent. One other property is the flexibility in preparing the volume of drug injected. Since botulinum toxin, as it is currently available (as BOTOX-A®) in the United States, requires reconstitution with preservative-free saline, there is flexibility for clinicians to manipulate the volume of solution that will be administered, without altering the dose.

We recently completed a trial comparing the effects of two volume preparations of BOTOX-A® on wrist and finger flexor spasticity of individuals with ABI. One group of patients received BOTOX-A® prepared as 100 units/cc, while another received BOTOX-A® prepared as 50 units/cc. Although there was no statistically significant difference between the two groups, there was a trend in favor of the group that received the higher volume, i.e.; they appeared to improve more based on decrease in muscle tone (measured by the Modified Ashworth Scale). This was compared by the clinician's global impression that the high volume group improved more. The latter measure achieved statistical significance. One possible reason for the absence of statistical significance was that the "high" volume (50 units/cc) was not high enough. Thus, we are proposing this study to investigate the comparative effects of three preparations of BOTOX-A®.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparative Efficacy of Three Preparations of Botox-A in Treating Spasticity
• Study Start Date: Jan 1, 2002
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 - Low Volume, High Dose Botox (onabotulinumtoxinA), 150 units prepared as 100 units per 1 ml of preservative-free normal saline	Drug: Botox; Botox 75-150 units, single treatment only; Other Names: generic name: botulinum toxin type A
Active Comparator: 2 - High Volume, High Dose Botox (onabotulinumtoxinA), 150 units prepared as 50 units per 1 ml of preservative-free normal saline	Drug: Botox; Botox 75-150 units, single treatment only; Other Names: generic name: botulinum toxin type A
Other: 3 - High Volume, Low Dose Botox (onabotulinumtoxinA), 75 units prepared as 25 units per 1 ml of preservative-free normal saline	Drug: Botox; Botox 75-150 units, single treatment only; Other Names: generic name: botulinum toxin type A

Outcome Measures

Primary Outcome Measures

1. Spastic Hypertonia as Measured by the Ashworth Scale [Baseline]

   The Ashworth Scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Score on the Ashworth scores ranges from 0-4, with 4 being the worst: 0 - No increase in muscle tone - Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension - More marked increase in muscle tone through most of the range of motion, but affected limb easily flexed - Considerable increase in muscle tone, passive movement difficult - Limb in flexion or extension

2. Spastic Hypertonia as Measured by the Ashworth Scale [Four weeks]

   The Ashworth Scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Score on the Ashworth scores ranges from 0-4, with 4 being the worst: 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension More marked increase in muscle tone through most of the range of motion, but affected limb easily flexed Considerable increase in muscle tone, passive movement difficult Limb in flexion or extension

3. Spastic Hypertonia as Measured by the Ashworth Scale [Eight Weeks]

   The Ashworth Scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Score on the Ashworth scores ranges from 0-4, with 4 being the worst: 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension More marked increase in muscle tone through most of the range of motion, but affected limb easily flexed Considerable increase in muscle tone, passive movement difficult Limb in flexion or extension

4. Spastic Hypertonia as Measured by the Ashworth Scale [Twelve Weeks]

   The Ashworth Scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Score on the Ashworth scores ranges from 0-4, with 4 being the worst: 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension More marked increase in muscle tone through most of the range of motion, but affected limb easily flexed Considerable increase in muscle tone, passive movement difficult Limb in flexion or extension

5. Spastic Hypertonia as Measured by the Ashworth Scale [Sixteen Weeks]

   The Ashworth Scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Score on the Ashworth scores ranges from 0-4, with 4 being the worst: 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension More marked increase in muscle tone through most of the range of motion, but affected limb easily flexed Considerable increase in muscle tone, passive movement difficult Limb in flexion or extension

Secondary Outcome Measures

1. Range of Motion as Measured by Goniometry [Baseline]

   This outcome reports the angle formed during ankle dorsiflexion by an imaginary line drawn on the outer side of the leg with an imaginary line drawn on the outside of the foot. The angle changes as the ankle is curled up (dorsiflexed) or down (plantarflexed). Many people with stroke develop muscle tightness (a condition called spasticity) or contracture, which leads to ankle plantarflexion and results in a "foot drop" appearance and limits range of motion. When the ankle is neutral and the foot is flat, the angle between the leg and the foot is roughly a right angle, and this neutral position is indicated as 0 degrees from the neutral position. If the foot is below the neutral position during maximum ankle dorsiflexion, then the angle reported is the number of degrees below the neutral position (reported as a negative value). If the foot is above the neutral position, then the angle reported is the number of degrees above the neutral position (positive value).

2. Range of Motion as Measured by Goniometry [8 weeks]

   This outcome reports the angle formed during ankle dorsiflexion by an imaginary line drawn on the outer side of the leg with an imaginary line drawn on the outside of the foot. The angle changes as the ankle is curled up (dorsiflexed) or down (plantarflexed). Many people with stroke develop muscle tightness (a condition called spasticity) or contracture, which leads to ankle plantarflexion and results in a "foot drop" appearance and limits range of motion. When the ankle is neutral and the foot is flat, the angle between the leg and the foot is roughly a right angle, and this neutral position is indicated as 0 degrees from the neutral position. If the foot is below the neutral position during maximum ankle dorsiflexion, then the angle reported is the number of degrees below the neutral position (reported as a negative value). If the foot is above the neutral position, then the angle reported is the number of degrees above the neutral position (positive value).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria -

• Spasticity resulting from ABI (stroke, including vascular malformations, traumatic brain injury)

• Ashworth Score (resting) of at least 2 of the primary ankle plantarflexor (gastrocnemius)

• Onset of primary illness at least six months prior to study inclusion

• At least 12 years of age

Exclusion Criteria -

• Hypersensitivity or allergy to botulinum toxin

• History of myasthenia gravis or other neuromuscular disease

• Current use of aminoglycosides

• Botulinum toxin or phenol injection to study limb within six months prior to recruitment

• Current use of other spasmolytic drug, such as diazepam, baclofen, dantrolene, tizanidine

• Presence of contracture or significant muscle atrophy

• Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kessler Institute for Rehabiliation	West Orange	New Jersey	United States	07052
2	Memorial Hermann Hospital	Houston	Texas	United States	77030

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston
• Allergan

Investigators

• Principal Investigator: Gerard E Francisco, MD, University of Texas

Study Documents (Full-Text)

None provided.

More Information

Publications

• Francisco GE, Boake C, Vaughn A. Botulinum toxin in upper limb spasticity after acquired brain injury: a randomized trial comparing dilution techniques. Am J Phys Med Rehabil. 2002 May;81(5):355-63.

• Responsible Party: Gerard Francisco, Clinical Professor and Chairman - Physical Medicine and Rehabilitation, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT00178646
• Other Study ID Numbers: HSC-MS-01-103
• First Posted: Sep 15, 2005
• Last Update Posted: Jan 22, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Gerard Francisco, Clinical Professor and Chairman - Physical Medicine and Rehabilitation, The University of Texas Health Science Center, Houston: Stroke; Brain Injuries; Spasticity; Botulinum Toxins
• Additional relevant MeSH terms: Muscle Spasticity; Brain Injuries; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Pre-assignment Detail	33 were enrolled but 32 started, and this is because one participant who enrolled decided not to start the study.

Arm/Group Title	Low Volume, High Dose	High Volume, High Dose	High Volume, Low Dose
Arm/Group Description	Botox, 150 units prepared as 100 units/ml Botox: Botox 75-150 units, single treatment only	Botox 150 units, prepared as 50 units/ml. Botox: Botox 75-150 units, single treatment only	Botox 75 units, prepared as 25 units/ml. Botox: Botox 75-150 units, single treatment only
Period Title: Overall Study
STARTED	12	9	11
COMPLETED	12	8	10
NOT COMPLETED	0	1	1

Baseline Characteristics

Arm/Group Title	Low Volume, High Dose	High Volume, High Dose	Low Volume, Low Dose	Total
Arm/Group Description	Botox, 150 units prepared as 100 units/ml Botox: Botox 75-150 units, single treatment only	Botox 150 units, prepared as 50 units/ml. Botox: Botox 75-150 units, single treatment only	Botox 75 units, prepared as 25 units/ml. Botox: Botox 75-150 units, single treatment only	Total of all reporting groups
Overall Participants	12	9	11	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	9 100%	11 100%	32 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 16.7%	4 44.4%	3 27.3%	9 28.1%
Male	10 83.3%	5 55.6%	8 72.7%	23 71.9%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Spastic Hypertonia as Measured by the Ashworth Scale
Description	The Ashworth Scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Score on the Ashworth scores ranges from 0-4, with 4 being the worst: 0 - No increase in muscle tone - Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension - More marked increase in muscle tone through most of the range of motion, but affected limb easily flexed - Considerable increase in muscle tone, passive movement difficult - Limb in flexion or extension
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Volume, High Dose	High Volume, High Dose	High Volume, Low Dose
Arm/Group Description	Botox, 150 units prepared as 100 units/ml Botox: Botox 75-150 units, single treatment only	Botox 150 units, prepared as 50 units/ml. Botox: Botox 75-150 units, single treatment only	Botox 75 units, prepared as 25 units/ml. Botox: Botox 75-150 units, single treatment only
Measure Participants	12	9	11
Mean (Full Range) [score on a scale]	2.4	2.33	2.36

2. Primary Outcome

Title	Spastic Hypertonia as Measured by the Ashworth Scale
Description	The Ashworth Scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Score on the Ashworth scores ranges from 0-4, with 4 being the worst: 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension More marked increase in muscle tone through most of the range of motion, but affected limb easily flexed Considerable increase in muscle tone, passive movement difficult Limb in flexion or extension
Time Frame	Four weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Volume, High Dose	High Volume, High Dose	High Volume, Low Dose
Arm/Group Description	Low volume, High Dose: Botox, 150 units prepared as 100 units/ml Botox: Botox 75-150 units, single treatment only	High volume, High Dose: Botox 150 units, prepared as 50 units/ml. Botox: Botox 75-150 units, single treatment only	HIgh Volume, Low Dose: Botox 75 units, prepared as 25 units/ml. Botox: Botox 75-150 units, single treatment only
Measure Participants	12	9	11
Mean (Full Range) [score on a scale]	2.42	2.56	2.36

3. Primary Outcome

Title	Spastic Hypertonia as Measured by the Ashworth Scale
Description	The Ashworth Scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Score on the Ashworth scores ranges from 0-4, with 4 being the worst: 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension More marked increase in muscle tone through most of the range of motion, but affected limb easily flexed Considerable increase in muscle tone, passive movement difficult Limb in flexion or extension
Time Frame	Eight Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Volume, High Dose	High Volume, High Dose	High Volume, Low Dose
Arm/Group Description	Botox, 150 units prepared as 100 units/ml Botox: Botox 75-150 units, single treatment only	Botox 150 units, prepared as 50 units/ml. Botox: Botox 75-150 units, single treatment only	Botox 75 units, prepared as 25 units/ml. Botox: Botox 75-150 units, single treatment only
Measure Participants	12	9	11
Mean (Full Range) [score on a scale]	1.42	0.77	1

4. Primary Outcome

Title	Spastic Hypertonia as Measured by the Ashworth Scale
Description	The Ashworth Scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Score on the Ashworth scores ranges from 0-4, with 4 being the worst: 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension More marked increase in muscle tone through most of the range of motion, but affected limb easily flexed Considerable increase in muscle tone, passive movement difficult Limb in flexion or extension
Time Frame	Twelve Weeks

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 2 in the Low volume High Dose arm, 1 in the High volume High Dose arm, and 1 in the High Volume Low Dose arm.

Arm/Group Title	Low Volume, High Dose	High Volume, High Dose	High Volume, Low Dose
Arm/Group Description	Low volume, High Dose: Botox, 150 units prepared as 100 units/ml Botox: Botox 75-150 units, single treatment only	High volume, High Dose: Botox 150 units, prepared as 50 units/ml. Botox: Botox 75-150 units, single treatment only	HIgh Volume, Low Dose: Botox 75 units, prepared as 25 units/ml. Botox: Botox 75-150 units, single treatment only
Measure Participants	10	8	10
Mean (Full Range) [score on a scale]	1.3	1	1.7

5. Primary Outcome

Title	Spastic Hypertonia as Measured by the Ashworth Scale
Description	The Ashworth Scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Score on the Ashworth scores ranges from 0-4, with 4 being the worst: 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension More marked increase in muscle tone through most of the range of motion, but affected limb easily flexed Considerable increase in muscle tone, passive movement difficult Limb in flexion or extension
Time Frame	Sixteen Weeks

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 1 in the High volume High Dose arm and 1 in the High Volume Low Dose arm.

Arm/Group Title	Low Volume, High Dose	High Volume, High Dose	High Volume, Low Dose
Arm/Group Description	Low volume, High Dose: Botox, 150 units prepared as 100 units/ml Botox: Botox 75-150 units, single treatment only	High volume, High Dose: Botox 150 units, prepared as 50 units/ml. Botox: Botox 75-150 units, single treatment only	HIgh Volume, Low Dose: Botox 75 units, prepared as 25 units/ml. Botox: Botox 75-150 units, single treatment only
Measure Participants	12	8	10
Mean (Full Range) [score on a scale]	1.42	1.13	1.1

6. Secondary Outcome

Title	Range of Motion as Measured by Goniometry
Description	This outcome reports the angle formed during ankle dorsiflexion by an imaginary line drawn on the outer side of the leg with an imaginary line drawn on the outside of the foot. The angle changes as the ankle is curled up (dorsiflexed) or down (plantarflexed). Many people with stroke develop muscle tightness (a condition called spasticity) or contracture, which leads to ankle plantarflexion and results in a "foot drop" appearance and limits range of motion. When the ankle is neutral and the foot is flat, the angle between the leg and the foot is roughly a right angle, and this neutral position is indicated as 0 degrees from the neutral position. If the foot is below the neutral position during maximum ankle dorsiflexion, then the angle reported is the number of degrees below the neutral position (reported as a negative value). If the foot is above the neutral position, then the angle reported is the number of degrees above the neutral position (positive value).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Volume, High Dose	High Volume, High Dose	High Volume, Low Dose
Arm/Group Description	Botox, 150 units prepared as 100 units/ml Botox: Botox 75-150 units, single treatment only	Botox 150 units, prepared as 50 units/ml. Botox: Botox 75-150 units, single treatment only	Botox 75 units, prepared as 25 units/ml. Botox: Botox 75-150 units, single treatment only
Measure Participants	12	9	11
Mean (Standard Deviation) [degrees]	-9.42 (5.42)	-6.56 (9.96)	-19.64 (13.90)

7. Secondary Outcome

Title	Range of Motion as Measured by Goniometry
Description	This outcome reports the angle formed during ankle dorsiflexion by an imaginary line drawn on the outer side of the leg with an imaginary line drawn on the outside of the foot. The angle changes as the ankle is curled up (dorsiflexed) or down (plantarflexed). Many people with stroke develop muscle tightness (a condition called spasticity) or contracture, which leads to ankle plantarflexion and results in a "foot drop" appearance and limits range of motion. When the ankle is neutral and the foot is flat, the angle between the leg and the foot is roughly a right angle, and this neutral position is indicated as 0 degrees from the neutral position. If the foot is below the neutral position during maximum ankle dorsiflexion, then the angle reported is the number of degrees below the neutral position (reported as a negative value). If the foot is above the neutral position, then the angle reported is the number of degrees above the neutral position (positive value).
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Data were not collected for on in the Low volume, High Dose arm, one in the High volume, High Dose arm, and one in the High Volume, Low Dose arm.

Arm/Group Title	Low Volume, High Dose	High Volume, High Dose	High Volume, Low Dose
Arm/Group Description	Low volume, High Dose: Botox, 150 units prepared as 100 units/ml Botox: Botox 75-150 units, single treatment only	High volume, High Dose: Botox 150 units, prepared as 50 units/ml. Botox: Botox 75-150 units, single treatment only	HIgh Volume, Low Dose: Botox 75 units, prepared as 25 units/ml. Botox: Botox 75-150 units, single treatment only
Measure Participants	11	8	10
Mean (Standard Deviation) [degrees]	-1.82 (6.82)	2.25 (8.08)	-2.30 (6.57)

Adverse Events

Time Frame	Four months
Arm/Group Title	Low Volume, High Dose		High Volume, High Dose		Low Volume, Low Dose
Arm/Group Description	Botox, 150 units prepared as 100 units/ml Botox: Botox 75-150 units, single treatment only		Botox 150 units, prepared as 50 units/ml. Botox: Botox 75-150 units, single treatment only		Botox 75 units, prepared as 25 units/ml. Botox: Botox 75-150 units, single treatment only
All Cause Mortality
	Low Volume, High Dose		High Volume, High Dose		Low Volume, Low Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Low Volume, High Dose		High Volume, High Dose		Low Volume, Low Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/9 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Low Volume, High Dose		High Volume, High Dose		Low Volume, Low Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		2/9 (22.2%)		0/11 (0%)
Eye disorders
Visual Change	0/12 (0%)	0	1/9 (11.1%)	1	0/11 (0%)	0
Gastrointestinal disorders
Bowel urgency	0/12 (0%)	0	1/9 (11.1%)	1	0/11 (0%)	0
General disorders
Increased Salivation	0/12 (0%)	0	1/9 (11.1%)	1	0/11 (0%)	0
Musculoskeletal and connective tissue disorders
Foot pain	1/12 (8.3%)	1	0/9 (0%)	0	0/11 (0%)	0
Nervous system disorders
Altered Mental Status	0/12 (0%)	0	1/9 (11.1%)	1	0/11 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)	0	1/9 (11.1%)	1	0/11 (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.