Trial Outcomes & Findings for In-Office Tympanostomy Tube Placement in Children (OTTER) (NCT NCT03323736)

Last Updated: 2022-05-26

Results Overview

Count (and percentage) of subjects in the pivotal cohort with successful placement of Tusker Medical tympanostomy tubes in all indicated ears in an office procedure. Note: the primary endpoint applies only to the Pivotal Cohort, and not to the OR Lead-In or Office Lead-In cohorts.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

370 participants

Primary outcome timeframe

Day of Procedure (Day 0) Immediately following tube placement

Results posted on

2022-05-26

Participant Flow

Participant milestones

Participant milestones
Measure	Pivotal Cohort Active Tymbion iontophoresis and tube insertion in all ears indicated for tube placement using the Tube Delivery System (TDS) in office.	Office Lead-In Cohort Active Tymbion iontophoresis and tube insertion in all indicated ears using the Tube Delivery System in-office. Physician initial iontophoresis and tube insertion procedures (minimum of 2 subjects per investigator).	OR Lead-In Cohort Tube insertion using the Tube Delivery System (TDS) in all indicated ears in the operating room (OR). Physician initial tube insertion procedures using the TDS in the OR (minimum of 2 subjects per investigator).
Overall Study STARTED	241	59	70
Overall Study Treated	222	47	68
Overall Study COMPLETED	222	47	68
Overall Study NOT COMPLETED	19	12	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Pivotal Cohort Active Tymbion iontophoresis and tube insertion in all ears indicated for tube placement using the Tube Delivery System (TDS) in office.	Office Lead-In Cohort Active Tymbion iontophoresis and tube insertion in all indicated ears using the Tube Delivery System in-office. Physician initial iontophoresis and tube insertion procedures (minimum of 2 subjects per investigator).	OR Lead-In Cohort Tube insertion using the Tube Delivery System (TDS) in all indicated ears in the operating room (OR). Physician initial tube insertion procedures using the TDS in the OR (minimum of 2 subjects per investigator).
Overall Study Screen Failure	14	9	1
Overall Study Withdrawal Before Treatment	3	1	1
Overall Study Iontophoresis fill/no iontophoresis	2	2	0

Baseline Characteristics

In-Office Tympanostomy Tube Placement in Children (OTTER)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pivotal Cohort n=222 Participants Active Tymbion iontophoresis and tube insertion using the Tube Delivery System in-office. Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the Tube Delivery System in all ears indicated for tube placement.	Office Lead-In Cohort n=47 Participants Active Tymbion iontophoresis and tube insertion using the Tube Delivery System in-office. Physician initial in-office iontophoresis and tube insertion procedures (minimum of 2 subjects per investigator). Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the Tube Delivery System in all ears indicated for tube placement.	OR Lead-In Cohort n=68 Participants Tubes insertion using the Tube Delivery System in the operating room (OR). Physician initial tube insertion procedures in the OR (minimum of 2 subjects per investigator). Tube placement: Subjects will have tubes placed in the OR using the Tube Delivery System in all ears indicated for tube placement.	Total n=337 Participants Total of all reporting groups
Age, Continuous	4.7 years STANDARD_DEVIATION 3.18 • n=5 Participants	4.8 years STANDARD_DEVIATION 3.10 • n=7 Participants	3.4 years STANDARD_DEVIATION 2.55 • n=5 Participants	4.5 years STANDARD_DEVIATION 3.09 • n=4 Participants
Sex: Female, Male Female	93 Participants n=5 Participants	20 Participants n=7 Participants	28 Participants n=5 Participants	141 Participants n=4 Participants
Sex: Female, Male Male	129 Participants n=5 Participants	27 Participants n=7 Participants	40 Participants n=5 Participants	196 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	31 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants	51 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	191 Participants n=5 Participants	40 Participants n=7 Participants	54 Participants n=5 Participants	285 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	24 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	36 Participants n=4 Participants
Race (NIH/OMB) White	183 Participants n=5 Participants	35 Participants n=7 Participants	53 Participants n=5 Participants	271 Participants n=4 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Region of Enrollment Canada	3 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment United States	219 participants n=5 Participants	43 participants n=7 Participants	64 participants n=5 Participants	326 participants n=4 Participants

PRIMARY outcome

Timeframe: Day of Procedure (Day 0) Immediately following tube placement

Outcome measures

Outcome measures
Measure	Pivotal Cohort (6 Month to <5 Year Old Children) n=120 Participants Active Tymbion iontophoresis and tubes insertion using the Tube Delivery System in-office Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the tube delivery system in all ears indicated for tube placement.	Pivotal Cohort (5 Through 12 Year Old Children) n=102 Participants Active Tymbion iontophoresis and tubes insertion using the Tube Delivery System in-office Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the tube delivery system in all ears indicated for tube placement.
Procedural Success:	103 Participants	91 Participants

PRIMARY outcome

Timeframe: Day of Procedure (Day 0) Immediately following tube placement

Population: Subjects with successful tube placement only. Note - 2 subjects were excluded from analysis because they did not self-report their pain scores, resulting in 89 participants analyzed.

Mean subject-reported pain score following TDS tube placement using the Faces Pain Scale-Revised (FPS-R) (pivotal cohort children ages 5 and older only). The FPS-R has 6 faces which permits scaling to a 0-to-10 scoring system in intervals of 2 (ie 0, 2, 4, 6, 8 and 10), where 0 represents 'no pain' and 10 represents 'very much pain'. Note- the primary endpoint applies only to the Pivotal Cohort, and not to the OR Lead-In or Office Lead-In cohorts.

Outcome measures

Outcome measures
Measure	Pivotal Cohort (6 Month to <5 Year Old Children) n=89 Participants Active Tymbion iontophoresis and tubes insertion using the Tube Delivery System in-office Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the tube delivery system in all ears indicated for tube placement.	Pivotal Cohort (5 Through 12 Year Old Children) Active Tymbion iontophoresis and tubes insertion using the Tube Delivery System in-office Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the tube delivery system in all ears indicated for tube placement.
Tube Placement Tolerability	3.30 score on a scale Standard Deviation 3.39	—

SECONDARY outcome

Timeframe: 3 Weeks Post Procedure

Count (and percentage) of subjects in the pivotal cohort, in which a Tusker Medical tube was successfully placed, with functionally patent tube(s) at the 3-week post-procedure follow-up visit. Note- thus secondary endpoint applies only to the Pivotal Cohort, and not to the OR Lead-In or Office Lead-In cohorts. Note - This endpoint includes subjects for which at least 1 ear had successful tube placement. For bilateral subjects, they may be considered a non-successful procedure if only 1 ear had successful tube placement, however would be evaluated for the Tube Patency endpoint for the ear that was successful.

Outcome measures

Outcome measures
Measure	Pivotal Cohort (6 Month to <5 Year Old Children) n=208 Participants Active Tymbion iontophoresis and tubes insertion using the Tube Delivery System in-office Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the tube delivery system in all ears indicated for tube placement.	Pivotal Cohort (5 Through 12 Year Old Children) Active Tymbion iontophoresis and tubes insertion using the Tube Delivery System in-office Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the tube delivery system in all ears indicated for tube placement.
Tube Patency	191 Participants	—

SECONDARY outcome

Timeframe: 3 Weeks Post Procedure

Count (percentage) of subjects in the pivotal cohort, in which a Tusker Medical tube(s) was successfully placed, with presence of a Tusker Medical tube across the TM in all successfully treated ears at the 3-week post-procedure follow-up visit. Note- the secondary endpoint applies only to the Pivotal Cohort, and not to the OR Lead-In or Office Lead-In cohorts. Note - This endpoint includes subjects for which at least 1 ear had successful tube placement. For bilateral subjects, they may be considered a non-successful procedure if only 1 ear had successful tube placement, however would be evaluated for the Tube Retention endpoint for the ear that was successful.

Outcome measures

Outcome measures
Measure	Pivotal Cohort (6 Month to <5 Year Old Children) n=208 Participants Active Tymbion iontophoresis and tubes insertion using the Tube Delivery System in-office Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the tube delivery system in all ears indicated for tube placement.	Pivotal Cohort (5 Through 12 Year Old Children) Active Tymbion iontophoresis and tubes insertion using the Tube Delivery System in-office Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the tube delivery system in all ears indicated for tube placement.
Tube Retention	206 Participants	—

SECONDARY outcome

Timeframe: Day of Procedure (Day 0)

Count (percentage) of subjects in the pivotal cohort, who completed iontophoresis for all indicated ears, with adequate anesthesia for TT placement in all treated ears as determined by physician's evaluation of TM anesthesia prior to tube placement. Note- the secondary endpoint applies only to the Pivotal Cohort, and not to the OR Lead-In or Office Lead-In cohorts.

Outcome measures

Outcome measures
Measure	Pivotal Cohort (6 Month to <5 Year Old Children) n=220 Participants Active Tymbion iontophoresis and tubes insertion using the Tube Delivery System in-office Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the tube delivery system in all ears indicated for tube placement.	Pivotal Cohort (5 Through 12 Year Old Children) Active Tymbion iontophoresis and tubes insertion using the Tube Delivery System in-office Iontophoresis \& tube placement: Subjects will receive active Tymbion iontophoresis and will have tubes placed in-office using the tube delivery system in all ears indicated for tube placement.
Anesthesia Effectiveness	206 Participants	—

Adverse Events

OR Lead-In Cohort (Subjects Treated in OR)

Serious events: 4 serious events

Other events: 28 other events

Deaths: 0 deaths

Office Lead-In Cohort (Subjects Treated in Office)

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Pivotal Cohort (Subjects Treated in Office)

Serious events: 3 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OR Lead-In Cohort (Subjects Treated in OR) n=68 participants at risk Tube insertion using the Tube Delivery System (TDS) in all indicated ears in the operating room (OR). Physician initial tube insertion procedures using the TDS in the OR (minimum of 2 subjects per investigator).	Office Lead-In Cohort (Subjects Treated in Office) n=47 participants at risk Active Tymbion iontophoresis and tube insertion in all ears indicated for tube placement using the Tube Delivery System (TDS) in office. Physician initial tube insertion procedures using the Iontophoresis System and the TDS in the Office (minimum of 2 subjects per investigator).	Pivotal Cohort (Subjects Treated in Office) n=222 participants at risk Active Tymbion iontophoresis and tube insertion in all ears indicated for tube placement using the Tube Delivery System (TDS) in office.
Respiratory, thoracic and mediastinal disorders Respiratory Syncytial Virus Infection	2.9% 2/68 • Number of events 2 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.00% 0/47 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.45% 1/222 • Number of events 1 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Musculoskeletal and connective tissue disorders Wrist Fracture	1.5% 1/68 • Number of events 1 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.00% 0/47 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.00% 0/222 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Gastrointestinal disorders Constipation	0.00% 0/68 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.00% 0/47 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.45% 1/222 • Number of events 1 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Respiratory, thoracic and mediastinal disorders Influenza	0.00% 0/68 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.00% 0/47 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.45% 1/222 • Number of events 1 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/68 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.00% 0/47 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.90% 2/222 • Number of events 2 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Respiratory, thoracic and mediastinal disorders Velopharyngeal Insufficiency	1.5% 1/68 • Number of events 1 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.00% 0/47 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.00% 0/222 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.

Other adverse events

Additional Information

Laura England, PhD

Smith+Nephew

Phone: (650) 223-6909

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI must submit communications to Sponsor for review and comment to verify accurate content at least 30 days prior to submitting to any third party. A delay up to 90 days may be requested by Sponsor in order to file patent applications relating to an Invention if applicable. Sponsor and PI agree that any Institution Publication shall only be made after the Multicenter Publication, provided that the Multicenter Publication is submitted within 18 months after conclusion of the study at all sites.
Publication restrictions are in place

Restriction type: OTHER

Measure	OR Lead-In Cohort (Subjects Treated in OR) n=68 participants at risk Tube insertion using the Tube Delivery System (TDS) in all indicated ears in the operating room (OR). Physician initial tube insertion procedures using the TDS in the OR (minimum of 2 subjects per investigator).	Office Lead-In Cohort (Subjects Treated in Office) n=47 participants at risk Active Tymbion iontophoresis and tube insertion in all ears indicated for tube placement using the Tube Delivery System (TDS) in office. Physician initial tube insertion procedures using the Iontophoresis System and the TDS in the Office (minimum of 2 subjects per investigator).	Pivotal Cohort (Subjects Treated in Office) n=222 participants at risk Active Tymbion iontophoresis and tube insertion in all ears indicated for tube placement using the Tube Delivery System (TDS) in office.
Ear and labyrinth disorders Inadequate Anesthesia	0.00% 0/68 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	8.5% 4/47 • Number of events 4 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	3.6% 8/222 • Number of events 8 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Ear and labyrinth disorders Occluded Tube	19.1% 13/68 • Number of events 15 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	10.6% 5/47 • Number of events 6 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	23.0% 51/222 • Number of events 65 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Ear and labyrinth disorders Otorrhea	27.9% 19/68 • Number of events 29 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	14.9% 7/47 • Number of events 14 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	27.0% 60/222 • Number of events 97 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Ear and labyrinth disorders Ear Pain	8.8% 6/68 • Number of events 6 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	19.1% 9/47 • Number of events 9 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	13.1% 29/222 • Number of events 32 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Ear and labyrinth disorders Otitis Media	19.1% 13/68 • Number of events 25 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	23.4% 11/47 • Number of events 14 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	27.5% 61/222 • Number of events 77 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	13.2% 9/68 • Number of events 12 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	6.4% 3/47 • Number of events 3 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	8.1% 18/222 • Number of events 21 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Respiratory, thoracic and mediastinal disorders Acute Sinusitis	5.9% 4/68 • Number of events 4 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	2.1% 1/47 • Number of events 2 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	7.2% 16/222 • Number of events 18 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Respiratory, thoracic and mediastinal disorders Pharyngitis Streptococcal	4.4% 3/68 • Number of events 3 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	8.5% 4/47 • Number of events 4 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	7.7% 17/222 • Number of events 17 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Ear and labyrinth disorders Ear infection	8.8% 6/68 • Number of events 9 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	8.5% 4/47 • Number of events 7 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	5.4% 12/222 • Number of events 15 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	8.8% 6/68 • Number of events 8 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	8.5% 4/47 • Number of events 13 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	4.5% 10/222 • Number of events 14 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Respiratory, thoracic and mediastinal disorders Croup	5.9% 4/68 • Number of events 6 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.00% 0/47 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	0.90% 2/222 • Number of events 3 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Ear and labyrinth disorders Middle ear effusion	2.9% 2/68 • Number of events 2 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	8.5% 4/47 • Number of events 6 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	6.8% 15/222 • Number of events 15 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Ear and labyrinth disorders Otitis externa	1.5% 1/68 • Number of events 1 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	6.4% 3/47 • Number of events 10 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	3.2% 7/222 • Number of events 8 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
General disorders Fever	0.00% 0/68 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	6.4% 3/47 • Number of events 3 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	2.7% 6/222 • Number of events 7 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Respiratory, thoracic and mediastinal disorders Cough	2.9% 2/68 • Number of events 2 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	8.5% 4/47 • Number of events 4 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	2.7% 6/222 • Number of events 6 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.
Respiratory, thoracic and mediastinal disorders Influenza	4.4% 3/68 • Number of events 3 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	6.4% 3/47 • Number of events 3 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.	2.7% 6/222 • Number of events 6 • Procedure through most recent follow-up visit with mean follow-up of 14.3 months (all cohorts combined). Individual cohort mean follow-up time is 11.3 months for OR Lead-In Cohort, 14.1 months for Office Lead-In Cohort, and 15.3 months for Pivotal Cohort.