Otiprio Versus Ciprodex Tympanostomy Tube Outcomes

Otiprio Versus Ciprodex to Reduce Tympanostomy Tube Failure

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.

Study Overview

• Status: Withdrawn
• Conditions: Otitis Media With Effusion in Children; Otorrhea
• Intervention / Treatment: Drug: Otiprio; Drug: Ciprodex

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 8 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Otiprio by surgeon; Otiprio will be administered through the tympanic membrane by the otolaryngologist immediately after tympanostomy placement.	Drug: Otiprio; 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.; Other Names: ciprofloxacin otic suspension
Active Comparator: Ciprodex by surgeon; Ciprodex drops will be instilled by the otolaryngologist into the affected ear immediately after tympanostomy surgery.	Drug: Ciprodex; 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; Other Names: ciprofloxacin and dexamethasone
Active Comparator: Ciprodex by surgeon and parent; 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; 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; Other Names: ciprofloxacin and dexamethasone

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Investigators: Study Chair: Peter Weber, MD, Boston Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2018
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: November 16, 2017
• First Submitted That Met QC Criteria: November 16, 2017
• First Posted (Actual): November 20, 2017

Study Record Updates

• Last Update Posted (Actual): September 14, 2018
• Last Update Submitted That Met QC Criteria: September 12, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Tympanostomy tube placement; Middle ear; Otiprio; Ciprodex drops; Ear drops
• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Ear Diseases; Otitis; Otitis Media; Otitis Media with Effusion; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Dexamethasone; Ciprofloxacin
• Other Study ID Numbers: H-37078

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes