Reduced Clavulanate Formulation of Amoxicillin-Clavulanate in Children 6-23 Months With Acute Otitis Media

NCT02630992 | Completed Phase 3 Results

• 1 other identifier: PRO15080192
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety profile of amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 90/3.2 mg/kg/day (formulation 1) or at 80/2.85 mg/kg/day (formulation 2) in two divided doses for 10 days. Investigators will focus on the proportion of subjects who develop protocol-defined diarrhea and proportion who develop diaper dermatitis that occasions the prescription of antifungal medication.

Conditions

Acute Otitis Media

Keywords

ear infections; antibiotics; antibiotic resistance; pediatrics; infants; children; amoxicillin-clavulanate

Outcome Measures

Primary Outcomes (4)

• The Distribution of Participants Receiving Formulation 1 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product

  Participants receiving formulation 1 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 90/3.2 mg/kg/day in two divided doses for 10 days. Protocol-defined diarrhea is defined as the occurrence of three or more watery stools in 1 day or two watery stools daily for 2 consecutive days and is limited to events associated with study product.

  Day 1 of administration of amoxicillin-clavulanate until day 12.

• The Distribution of Participants Receiving Formulation 2 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product

  Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Protocol-defined diarrhea is defined as the occurrence of three or more watery stools in 1 day or two watery stools daily for 2 consecutive days and is limited to events associated with study product.

  Day 1 of administration of amoxicillin-clavulanate until day 12.

• The Distribution of Participants Receiving Formulation 1 for Whom Diaper Dermatitis Was Reported and Associated With Study Product

  Participants receiving formulation 1 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 90/3.2 mg/kg/day in two divided doses for 10 days. Diaper dermatitis is defined as dermatitis in the diaper area calling for prescription of a topical antifungal agent and is limited to events associated with study product.

  Day 1 of administration of amoxicillin-clavulanate until day 12.

• The Distribution of Participants Receiving Formulation 2 for Whom Diaper Dermatitis Was Reported and Associated With Study Product

  Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Diaper dermatitis is defined as dermatitis in the diaper area calling for prescription of a topical antifungal agent and is limited to events associated with study product..

  Day 1 of administration of amoxicillin-clavulanate until day 12.

Secondary Outcomes (10)

• The Distribution of Participants Receiving Formulation 1 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit

  From 72 hours after the initial AOM until the end-of-treatment visit. The mean day for this visit was 14.9.

• The Distribution of Participants Receiving Formulation 2 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit

  From 72 hours after the initial AOM until the end-of-treatment visit. The mean day for this visit was 13.9.

• The Distribution of Participants Receiving Formulation 1 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit

  Day 1 of administration of amoxicillin-clavulanate until the day 7 visit. The mean day for this visit was 7.5.

• The Distribution of Participants Receiving Formulation 2 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit

  Day 1 of administration of amoxicillin-clavulanate until the day 7 visit. The mean day for this visit was 7.6.

• The Mean Score Representing the Parent or Guardian's Level of Satisfaction With Therapy for Participants Receiving Formulation 1

  The end-of-treatment visit. The mean day for this visit was 14.9.

Study Arms (1)

amoxicillin-clavulanate potassium

EXPERIMENTAL

amoxicillin-clavulanate potassium (600 mg/221.5 mg/5 mL; 28:1) administered prior to February 25, 2016 at 90/3.2 mg/kg/day in two divided doses for 10 days; oral, liquid (formulation 1) or administered as of February 25, 2016 at 80/2.85 mg/kg/day in two divided doses for 10 days; oral, liquid (formulation 2)

Drug: Amoxicillin-Clavulanate potassium

Interventions

Amoxicillin-Clavulanate potassium DRUG

Also known as: Augmentin

amoxicillin-clavulanate potassium

Eligibility Criteria

• Age: 6 Months - 23 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age range: 6 to 23 months
• Evidence of AOM
• Recent (within 48 hours) onset of signs and symptoms.
• Middle ear effusion evidenced by the presence of at least 2 of the following: decreased or absent mobility of the tympanic membrane (TM), yellow of white discoloration of the TM, and/or opacification of the TM
• Acute inflammation evidenced by one of the following: 1+ bulging of the TM with either intense erythema or otalgia or 2+ or 3+ bulging of the TM

You may not qualify if:

• Toxic appearance (capillary refill \>3 seconds, systolic blood pressure \<60 mm Hg)
• Inpatient hospitalization
• Clinical or anatomical characteristics that might obscure response to treatment (e.g., tympanostomy tubes in place, cleft palate, Down syndrome)
• Sensorineural hearing loss (unilateral or bilateral)
• Allergy to amoxicillin or amoxicillin clavulanate
• Recent treatment of AOM within the last 14 days

Sponsors & Collaborators

• Nader Shaikh: lead

Study Sites (1)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Hoberman A, Paradise JL, Rockette HE, Jeong JH, Kearney DH, Bhatnagar S, Shope TR, Muniz G, Martin JM, Kurs-Lasky M, Haralam M, Pope MA, Nagg JP, Zhao W, Miah MK, Beumer J, Venkataramanan R, Shaikh N. Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media. Antimicrob Agents Chemother. 2017 Jun 27;61(7):e00238-17. doi: 10.1128/AAC.00238-17. Print 2017 Jul.

  PMID: 28438923 DERIVED

MeSH Terms

Conditions

Otitis Media; Otitis

Interventions

Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Ear Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Nader Shaikh
• Organization: University of Pittsburgh

nader.shaikh@chp.edu

412-692-8111

Study Officials

• Nader Shaikh, MD, MPH

  University of Pittsburgh School of Medicine; Children's Hospital of Pittsburgh of UPMC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: December 11, 2015
• First Posted: December 15, 2015
• Study Start: December 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: July 1, 2017
• Last Updated: January 3, 2018
• Results First Posted: January 3, 2018

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)