Otiprio Versus Ciprodex Tympanostomy Tube Outcomes

Study Overview
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Brief Summary
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Otolaryngologists routinely administer ear drops at the time of tympanostomy tube placement in order to prevent tube otorrhea; however, there is a lack of consensus as to which drops are the most effective, and whether a post-operative regimen should be used. Utilizing drops postoperatively places the onus of administration on parents who may have various difficulties in delivering the drops to their child's ears. Additionally, prescribing drops postoperatively is a health care cost. The purpose of this study is to determine if there is a difference in prevention of tympanostomy tube failure (defined as tube blockage or otorrhea) between Otiprio administered once intraoperatively, Ciprodex otic dropgs administered once intraoperatively, and Ciprodex otic drops administered intraoperatively with a postoperative course.

Detailed Description
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Tympanostomy tube placement is indicated in children with recurrent acute otitis media or chronic otitis media with effusion. Ear dishcarge, otorrhea, is the most common complication following tympanostomy tube placement and occurs in up to 25% of patients. Otorrhea can lead to tube obstruction, making the tube ineffective in ventilating the middle ear or improving hearing. Otolaryngologists routinely administer ear drops at the time of tympanostomy tube placement in order to prevent otorrhea and tube blockage; however, there is lack of consensus as to which drops are the most effective and what dosing regimen should be used. Options for prevention of otorrhea and tympanostomy tube blockage include intraoperative single-dose application of topical drops or postoperative prolonged application of topical drops. One issue with the prolonged application of drops after surgery is the requirement of parents to administer the drops at home. Thus, the delivery of medication to the middle ear is variable given the difficulty of administering ear drops to a child. Another option exists as a one-time application at the time of surgery, but provides an extended duration of medication in the middle ear. Otiprio is a single-dose suspension of ciprofloxacin and has been FDA approved since February 2015 for use in pediatric patients with otitis media with effusion who require tympanostomy tube placement. Otiprio exists as a liquid at or below room temperature and transitions into a gel after exposure to body temperature in the middle ear. Administrated as an injection into the middle ear at the time of tympanostomy tube placement, Otipiro slowly releases antibiotic treatment over the course of a week, eliminating the need for parents to administer drops. The study is a prospective, randomized (1:1:1), single-blind, trial of three treatment groups in pediatric subjects with bilateral middle ear effusion who require tympanostomy tube placement. Approximately 300 subjects will be randomized: 100 randomized to receive Otiprio intraoperatively, 100 randomized to receive Ciprodex intraoperatively, and 100 randomized to receive Ciprodex intraoperatively with five days of Ciprodex drops postoperatively. All participants will undergo tympanostomy tube placement in the operating room as clinically indicated by an Otolaryngologist. Prior to the surgery, the patient will be randomized to one of the three trial arms. During the operation, the surgeon, who will be blinded until completion of tube placement as to which arm the participant is randomized, will administer Otiprio as a one-time intratympanic injection or Ciprodex, by administering 3-5 drops into each ear canal. For the trial arm that includes a 5 day course of Ciprodex postoperatively, the patient's parents will be instructed on how to administer the drops. As per standard of care, all participants will be assessed at a postoperative visit 2-4 weeks post surgery. A blinded assessor to the randomized study arm will perform otoscopy (ear exam) during that visit to determine if there is presence of otorrhea or tympanostomy tube blockage.

Official Title
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Otiprio Versus Ciprodex to Reduce Tympanostomy Tube Failure

Conditions
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Otorrhea, Otitis Media With Effusion in Children

Intervention / Treatment
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* Drug: Otiprio
* Drug: Ciprodex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children (6 months to 10 years) Clinical diagnosis of bilateral middle ear effusion or recurrent acute otitis media requiring tympanostomy tube placement Exclusion Criteria: Patient having any other concurrent surgery History of mastoid surgery, chronic or recurrent bacterial infections Tympanic membrane perforations History of immunodeficiency disease Abnormalities of the tympanic membrane or middle ear Otic or systemic corticosteroid within 7 days of surgery Topical or systemic antimicrobials or antifungal agents prior to their particular washout intervals Concurrent use of anti-inflammatory agents Allergy to the medications used in this study and their components Menarcheal or postmenarcheal female.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Otiprio by surgeon<br>Otiprio will be administered through the tympanic membrane by the otolaryngologist immediately after tympanostomy placement. | Drug: Otiprio<br>* Otiprio is a single-dose, physician-administered, sustained-exposure otic fluoroquinolone antibacterial for the treatment of pediatric patients with bilateral otitis media with effusion undergoing tympanostomy tube placement surgery. Otoprio (6% ciprofloxacin, 60 mg/mL) will be administered through the tube lumen by the otolaryngologist immediately after tympanostomy surgery.<br>* Other names: ciprofloxacin otic suspension;|
| Active Comparator: Ciprodex by surgeon<br>Ciprodex drops will be instilled by the otolaryngologist into the affected ear immediately after tympanostomy surgery. | Drug: Ciprodex<br>* Ciprodex is a combined antibiotic and steroid ear drop used to treat otitis media with tympanostomy tubes. Four drops of Ciprodex (0.14mL) instilled by the otolaryngologist into the affected ear immediately after tympanostomy surgery. Each mL of Ciprodex contains ciprofloxacin hydrochloride 0.3 % (equivalent to 3 mg ciprofloxacin base) and dexamethasone 0.1 % equivalent to 1 mg dexamethasone<br>* Other names: ciprofloxacin and dexamethasone;|
| Active Comparator: Ciprodex by surgeon and parent<br>Ciprodex drops will be instilled by the otolaryngologist into the ear immediately after tympanostomy tube surgery. The parent or guardian will administer Ciprodex drops into the ears twice daily for five days after surgery. | Drug: Ciprodex<br>* Ciprodex is a combined antibiotic and steroid ear drop used to treat otitis media with tympanostomy tubes. Four drops of Ciprodex (0.14mL) instilled by the otolaryngologist into the affected ear immediately after tympanostomy surgery. Each mL of Ciprodex contains ciprofloxacin hydrochloride 0.3 % (equivalent to 3 mg ciprofloxacin base) and dexamethasone 0.1 % equivalent to 1 mg dexamethasone<br>* Other names: ciprofloxacin and dexamethasone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post operative otorrhea | Otorrhea is drainage from the ear. Evaluation will be performed by a blind assessor via otoscopy. | Post operative visit 2-4 weeks after tube placement | 
| Tympanostomy tube blockage | Tympanostomy tube blockage is when the placed tube becomes clogged or obstructed. Evaluation will be performed by a blind assessor via otoscopy. | Post operative visit 2-4 weeks after tube placement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of effusion post operatively | Effusion is the presence of middle ear fluid. Evaluation will be performed by a blind assessor via otoscopy. | Post operative visit 2-4 weeks after tube placement | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tympanostomy tube placement, Otiprio, Ciprodex drops, Ear drops, Middle ear