AOM - Acute Otitis Media, OME - Otitis Media With Effusion
Conditions
Brief summary
A prospective, single-arm, multicenter study to evaluate effectiveness and safety of Tymbion iontophoresis and tympanostomy tube placement using the Tula Iontophoresis and Tube Delivery Systems for children in an office setting.
Detailed description
The objective of this study is to evaluate effectiveness and safety of tympanostomy tube (TT) placement in children following local anesthesia in a physician's clinic setting (henceforth referred to as 'in-office'). Local anesthesia using Tymbion, a lidocaine-based anesthetic, is delivered by the Tula Iontophoresis System (IPS) and TT placement is implemented by the Tula Tube Delivery System (TDS). The IPS will be used to facilitate anesthetic delivery to the tympanic membrane (TM). The Iontophoresis System consists of an Iontophoresis Control Unit, Iontophoresis Earsets and a return electrode patch. The Control Unit monitors and delivers a fixed amount of charge (ie, dose) to the patient through the Earsets(s) and alerts the operator when charge delivery is complete. The lidocaine-based solution used for local anesthesia of the TM is Tymbion (2% lidocaine HCl/ 1:100,000 epinephrine). The TDS is a mechanical device that integrates a myringotomy blade, tympanostomy tube and tube inserter for TT placement with a user-controlled activation. The study will use the TDS with a grommet-type tube. This pivotal study will include up to 422 children ages 6 months through 12 years indicated for tympanostomy tube placement enrolled at approximately 15 to 25 investigational centers in the US and Canada. The pivotal cohort consists of 222 subjects. In addition, up to 100 subjects will be enrolled as lead-in procedures in the OR using the TDS and up to 100 subjects will be enrolled as lead-in procedure in-office (using IPS and TDS) as the surgeons' initial experience with the technology prior to enrolling into the pivotal cohort. All pivotal and lead-in subjects will follow the same study protocol assessments and visit schedule consisting of a screening visit, procedure visit and 3-week, 6 month, 12 month, 18 month, and 24 month post-procedure follow-up visits. Lead-in procedures will be analyzed separately from the pivotal pediatric cohort.
Interventions
COMBINATION_PRODUCTIontophoresis & 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.
DEVICETube placement
Subjects will have tubes placed in the OR using the Tube Delivery System in all ears indicated for tube placement.
Sponsors
Tusker Medical
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Pivotal cohort is single arm. Physician initial subjects evaluated in separate cohorts but not included in primary and secondary analyses.
Eligibility
Sex/Gender
ALL
Age
6 Months to 12 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females at least 6 months old through 12 years old at time of consent 2. Indication for tympanostomy tube insertion per Clinical Practice Guideline 3. Behavioral capacity and cooperative temperament to undergo an awake procedure, based on physician judgment (not applicable to OR Lead-In subjects) 4. Subject's parent/guardian and subject are able and willing to comply with the protocol and attend all study visits 5. Subject's parent/guardian and subject are able and willing to provide informed consent or assent as age appropriate
Exclusion criteria
1. Significantly atrophic, retracted, bimeric, monomeric or atelectatic tympanic membrane 2. Perforated tympanic membrane 3. Otitis externa 4. Active or recent conditions of the tympanic membrane (eg, prior myringotomy with incomplete wound healing or re-epithelization) 5. Hemotympanum 6. Damaged/denuded skin in the auditory canal 7. Cerumen impaction resulting in a significant amount of cleaning required to visualize the tympanic membrane potentially causing abrasion or irritation to the external ear canal 8. Anatomy that precludes sufficient visualization of and access to the tympanic membrane 9. Anatomy that necessitates tympanostomy tube placement in the posterior half of the tympanic membrane 10. History of sensitivity or allergic reaction to lidocaine HCl, tetracaine, epinephrine, or any hypersensitivity to local anesthetics of the amide type, or any component of the anesthetic drug formulation (not applicable to OR Lead-In subjects) 11. Familial history of insensitivity to lidocaine or other local anesthetics of the amide type (eg, history of inadequate anesthesia with dental numbing agents). (not applicable to OR Lead-In subjects) 12. Electrically sensitive medical support systems (eg, pacemakers, defibrillators, cochlear implants) 13. Other conditions that would preclude performing the study procedure including iontophoresis system ear plug incompatibility. 14. Health conditions that, in the opinion of the investigator, would present undue risk to the subject, based on device/anesthetic drug product label warnings and precautions. 15. Subject is 4 years or older and not able to complete all baseline assessments. Subject is younger than 4 years and not able to complete all baseline assessments, not including audiometry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Procedural Success: | Day of Procedure (Day 0) Immediately following tube placement | 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. |
| Tube Placement Tolerability | Day of Procedure (Day 0) Immediately following tube placement | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tube Patency | 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. |
| Tube Retention | 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. |
| Anesthesia Effectiveness | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pivotal Cohort 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. | 222 |
| Office Lead-In Cohort 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. | 47 |
| OR Lead-In Cohort 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. | 68 |
| Total | 337 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Iontophoresis fill/no iontophoresis | 2 | 2 | 0 |
| Overall Study | Screen Failure | 14 | 9 | 1 |
| Overall Study | Withdrawal Before Treatment | 3 | 1 | 1 |
Baseline characteristics
| Characteristic | Pivotal Cohort | Total | OR Lead-In Cohort | Office Lead-In Cohort |
|---|---|---|---|---|
| Age, Continuous | 4.7 years STANDARD_DEVIATION 3.18 | 4.5 years STANDARD_DEVIATION 3.09 | 3.4 years STANDARD_DEVIATION 2.55 | 4.8 years STANDARD_DEVIATION 3.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 31 Participants | 51 Participants | 14 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 191 Participants | 285 Participants | 54 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 7 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 36 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 5 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 18 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) White | 183 Participants | 271 Participants | 53 Participants | 35 Participants |
| Region of Enrollment Canada | 3 participants | 11 participants | 4 participants | 4 participants |
| Region of Enrollment United States | 219 participants | 326 participants | 64 participants | 43 participants |
| Sex: Female, Male Female | 93 Participants | 141 Participants | 28 Participants | 20 Participants |
| Sex: Female, Male Male | 129 Participants | 196 Participants | 40 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 68 | 0 / 47 | 0 / 222 |
| other Total, other adverse events | 28 / 68 | 22 / 47 | 79 / 222 |
| serious Total, serious adverse events | 4 / 68 | 0 / 47 | 3 / 222 |
Outcome results
Primary
Procedural Success:
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.
Time frame: Day of Procedure (Day 0) Immediately following tube placement
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal Cohort (6 Month to <5 Year Old Children) | Procedural Success: | 103 Participants |
| Pivotal Cohort (5 Through 12 Year Old Children) | Procedural Success: | 91 Participants |
Comparison: Procedural success rate was compared to the performance goal of 68% using a Bayesian Hierarchical model.95% CI: [0.8, 0.91]
Comparison: Procedural success rate was compared to the performance goal of 68% using a Bayesian Hierarchical model.95% CI: [0.82, 0.93]
Primary
Tube Placement Tolerability
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pivotal Cohort (6 Month to <5 Year Old Children) | Tube Placement Tolerability | 3.30 score on a scale | Standard Deviation 3.39 |
p-value: 0.0072t-test, 1 sided
Secondary
Anesthesia Effectiveness
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.
Time frame: Day of Procedure (Day 0)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal Cohort (6 Month to <5 Year Old Children) | Anesthesia Effectiveness | 206 Participants |
Comparison: The Anesthesia Effectiveness endpoint would be successfully met if the percentage of subjects with successful anesthesia was greater than (superior to) 85% (by subject), at a significance level of 0.025 (p\<0.025).p-value: <0.0001mid-P method for single proportion
Secondary
Tube Patency
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.
Time frame: 3 Weeks Post Procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal Cohort (6 Month to <5 Year Old Children) | Tube Patency | 191 Participants |
Comparison: Tube Patency endpoint would be successfully met if the percentage of subjects with patent tubes was greater than (superior to) 80% (by subject), at a significance level of 0.025 (p\<0.025).p-value: <0.0001mid-P method for single proportion
Secondary
Tube Retention
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.
Time frame: 3 Weeks Post Procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal Cohort (6 Month to <5 Year Old Children) | Tube Retention | 206 Participants |
Comparison: Tube Retention endpoint would be successfully met if the percentage of subjects with retained tubes was greater than (superior to) 88% (by subject), at a significance level of 0.025 (p\<0.025).p-value: <0.0001mid-P method for single proportion