A Clinical Trial of Proton Pump Inhibitors to Treat Children With Chronic Otitis Media With Effusion

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT00546117
• Collaborator: Doris Duke Charitable Foundation (Other), TAP Pharmaceutical Products Inc. (Industry)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 26
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study is being done to see if reflux of stomach fluid might be a cause of chronic fluid in the ears. Our hypothesis is that treatment with an anti-reflux medication (lansoprazole) will increase the rate of resolution of chronic middle ear fluid in children.

Condition or Disease	Intervention/Treatment	Phase
Otitis Media With Effusion	Drug: lansoprazole; Drug: placebo	N/A

Detailed Description

This study is being done to see if reflux of stomach fluid might be a cause of fluid in the ears. Earlier studies have found pepsin or pepsinogen, a component of stomach fluid, in the middle ear fluid of many children with chronic middle ear fluid. Anti-reflux medicines called proton pump inhibitors (PPI) reduce the acidity of the contents of the stomach and the activity of pepsin or pepsinogen. We are studying the effectiveness of a PPI called lansoprazole (Prevacid™) in reducing fluid in the ears. If lansoprazole is able to reduce the fluid in the middle ear, this tells us that the reflux of gastric acid into the esophagus and into the ear canal may be causing middle ear fluid.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Clinical Trial of Proton Pump Inhibitors to Treat Children With Chronic Otitis Media With Effusion
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lansoprazole (Prevacid) Prevacid SoluTab (15 or 30 mg tab) once daily for 2 months	Drug: lansoprazole; Prevacid SoluTab 15 mg daily by mouth for 2 months (patients weighing 10-30 kg),or Prevacid SoluTab 30 mg daily by mouth for 2 months (patients weighing >30 kg) is the experimental arm. Placebo Solutabs will be given in the same dosage, frequency, and duration for the placebo arm.; Other Names: Prevacid SoluTab
Placebo Comparator: Placebo Placebo SoluTab once daily for 2 months	Drug: placebo; Placebo Solutab in 15 and 30 mg dosages.; Other Names: Placebo Solutab

Outcome Measures

Primary Outcome Measures

1. Absence of Middle Ear Fluid by Pneumatic Otoscopy, Right Ear [2 months]

2. Absence of Middle Ear Fluid by Pneumatic Otoscopy, LeftEar [2 months]

Secondary Outcome Measures

1. Acoustic Reflectometry: Level of Risk as Defined by Manufacturer [2 months]

   Spectral gradient acoustic reflectometry is a noninvasive, non-audible acoustic wave used to help detect middle ear fluid. The manufacturer recommends interpretation of the angle result as: <49°, high risk of middle ear effusion (level 5); 49-59°, moderate-high risk (level 4); 60-69°, moderate risk (level 3); 70-95°, low-moderate risk (level 2) and >95°, low risk (level 1).

2. Number of Participants With Normal Type A Tympanometry [2 months]

   Tympanometry of both ears, coded by Jerger classification (Type A, normal; type B, flat; Type C; negative pressure). This is a standard test of middle ear status as performed by audiologists. Please refer to the reference for more information: Kileny & Zwolan, Diagnostic Audiology, chapter 133, Cummings Otolaryngology-Head and Neck Surgery, Elsevier/Saunders, 2015.

3. Number of Participants With at Least 1 Symptoms of Reflux in the Past Week, Assessed by the Reflux Symptom Questionnaire [2 months]

   Questions regarding reflux symptoms, created and evaluated by Nelson et al, Prevalence of symptoms of gastroesophageal reflux during childhood: a pediatric practice-based survey, Arch Pediatr Adolesc Med 2000;154;150-154. This study used the GER3-9P version for children aged 3-9 years. Results are reported as number reporting at least one specific symptom in the past week, maximum 7 symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• History of chronic otitis media with effusion meeting clinical indications for tympanostomy tubes placement, defined as the presence of middle ear fluid on physical exam for at least 3 months, in at least one ear.

Exclusion Criteria:

• Past medical history or concurrent conditions known to increase the incidence of either recurrent otitis media or otitis media with effusion or gastroesophageal reflux disease, including cleft palate, neurological delay, cerebral palsy, Down syndrome, velocardiofacial syndrome, and primary ciliary dyskinesia.

• Children with structural abnormalities of the tympanic membranes, such as cholesteatoma, deep retraction pockets, and atelectasis of the tympanic membrane. These abnormalities would require placement of tympanostomy tubes in standard clinical practice.

• Children weighing less than 10 kilograms, due to the lower weight limit for standard Prevacid™ dosing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• Doris Duke Charitable Foundation
• TAP Pharmaceutical Products Inc.

Investigators

• Principal Investigator: Judith EC Lieu, MD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• Abd El-Fattah AM, Abdul Maksoud GA, Ramadan AS, Abdalla AF, Abdel Aziz MM. Pepsin assay: a marker for reflux in pediatric glue ear. Otolaryngol Head Neck Surg. 2007 Mar;136(3):464-70.
• Lieu JE, Muthappan PG, Uppaluri R. Association of reflux with otitis media in children. Otolaryngol Head Neck Surg. 2005 Sep;133(3):357-61.
• Sone M, Yamamuro Y, Hayashi H, Yanagi E, Niwa Y, Nakashima T. Prediction of gastroesophageal reflux in otitis media with effusion in adults. Acta Otolaryngol. 2007 May;127(5):470-3.
• Tasker A, Dettmar PW, Panetti M, Koufman JA, P Birchall J, Pearson JP. Is gastric reflux a cause of otitis media with effusion in children? Laryngoscope. 2002 Nov;112(11):1930-4.

• Responsible Party: Judith Lieu, Assistant Professor, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT00546117
• Other Study ID Numbers: HRPO# 07-0762
• First Posted: Oct 18, 2007
• Last Update Posted: Jun 1, 2018
• Last Verified: May 1, 2018

• Keywords provided by Judith Lieu, Assistant Professor, Washington University School of Medicine: otitis media with effusion; gastroesophageal reflux; ear infection; proton pump inhibitor
• Additional relevant MeSH terms: Otitis; Otitis Media; Otitis Media with Effusion; Lansoprazole; Dexlansoprazole

Study Results

Participant Flow

Arm/Group Title	Prevacid	Placebo
Arm/Group Description	Prevacid SoluTab (15 or 30 mg tab) once daily for 2 months	Placebo SoluTab once daily for 2 months
Period Title: Overall Study
STARTED	9	7
COMPLETED	5	7
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Prevacid	Placebo	Total
Arm/Group Description	Prevacid SoluTab (15 or 30 mg tab) once daily for 2 months	Placebo SoluTab once daily for 2 months	Total of all reporting groups
Overall Participants	9	7	16
Age (Count of Participants)
<=18 years	9 100%	7 100%	16 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	4.82 (1.98)	5.45 (1.32)	5.10 (1.86)
Sex: Female, Male (Count of Participants)
Female	5 55.6%	1 14.3%	6 37.5%
Male	4 44.4%	6 85.7%	10 62.5%
Region of Enrollment (participants) [Number]
United States	9 100%	7 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Absence of Middle Ear Fluid by Pneumatic Otoscopy, Right Ear
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prevacid	Placebo
Arm/Group Description	Prevacid SoluTab (15 or 30 mg tab) once daily for 2 months	Placebo SoluTab once daily for 2 months
Measure Participants	9	7
Number [participants]	1 11.1%	0 0%

2. Primary Outcome

Title	Absence of Middle Ear Fluid by Pneumatic Otoscopy, LeftEar
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prevacid	Placebo
Arm/Group Description	Prevacid SoluTab (15 or 30 mg tab) once daily for 2 months	Placebo SoluTab once daily for 2 months
Measure Participants	9	7
Number [participants]	1 11.1%	3 42.9%

3. Secondary Outcome

Title	Acoustic Reflectometry: Level of Risk as Defined by Manufacturer
Description	Spectral gradient acoustic reflectometry is a noninvasive, non-audible acoustic wave used to help detect middle ear fluid. The manufacturer recommends interpretation of the angle result as: <49°, high risk of middle ear effusion (level 5); 49-59°, moderate-high risk (level 4); 60-69°, moderate risk (level 3); 70-95°, low-moderate risk (level 2) and >95°, low risk (level 1).
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lansoprazole (Prevacid)	Placebo
Arm/Group Description	Prevacid SoluTab (15 or 30 mg tab) once daily for 2 months lansoprazole: Prevacid SoluTab 15 mg daily by mouth for 2 months (patients weighing 10-30 kg),or Prevacid SoluTab 30 mg daily by mouth for 2 months (patients weighing >30 kg) is the experimental arm. Placebo Solutabs will be given in the same dosage, frequency, and duration for the placebo arm.	Placebo SoluTab once daily for 2 months placebo: Placebo Solutab in 15 and 30 mg dosages.
Measure Participants	9	7
Mean (Full Range) [level of risk]	2.5	3.5

4. Secondary Outcome

Title	Number of Participants With Normal Type A Tympanometry
Description	Tympanometry of both ears, coded by Jerger classification (Type A, normal; type B, flat; Type C; negative pressure). This is a standard test of middle ear status as performed by audiologists. Please refer to the reference for more information: Kileny & Zwolan, Diagnostic Audiology, chapter 133, Cummings Otolaryngology-Head and Neck Surgery, Elsevier/Saunders, 2015.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lansoprazole (Prevacid)	Placebo
Arm/Group Description	Prevacid SoluTab (15 or 30 mg tab) once daily for 2 months lansoprazole: Prevacid SoluTab 15 mg daily by mouth for 2 months (patients weighing 10-30 kg),or Prevacid SoluTab 30 mg daily by mouth for 2 months (patients weighing >30 kg) is the experimental arm. Placebo Solutabs will be given in the same dosage, frequency, and duration for the placebo arm.	Placebo SoluTab once daily for 2 months placebo: Placebo Solutab in 15 and 30 mg dosages.
Measure Participants	9	7
Count of Participants [Participants]	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants With at Least 1 Symptoms of Reflux in the Past Week, Assessed by the Reflux Symptom Questionnaire
Description	Questions regarding reflux symptoms, created and evaluated by Nelson et al, Prevalence of symptoms of gastroesophageal reflux during childhood: a pediatric practice-based survey, Arch Pediatr Adolesc Med 2000;154;150-154. This study used the GER3-9P version for children aged 3-9 years. Results are reported as number reporting at least one specific symptom in the past week, maximum 7 symptoms.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lansoprazole (Prevacid)	Placebo
Arm/Group Description	Prevacid SoluTab (15 or 30 mg tab) once daily for 2 months lansoprazole: Prevacid SoluTab 15 mg daily by mouth for 2 months (patients weighing 10-30 kg),or Prevacid SoluTab 30 mg daily by mouth for 2 months (patients weighing >30 kg) is the experimental arm. Placebo Solutabs will be given in the same dosage, frequency, and duration for the placebo arm.	Placebo SoluTab once daily for 2 months placebo: Placebo Solutab in 15 and 30 mg dosages.
Measure Participants	9	7
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Arm/Group Title	Prevacid		Placebo
Arm/Group Description	Prevacid SoluTab (15 or 30 mg tab) once daily for 2 months		Placebo SoluTab once daily for 2 months
All Cause Mortality
	Prevacid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/7 (0%)
Serious Adverse Events
	Prevacid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Prevacid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.