Clinical trial NCT04804098: Effect of Rate (Slope) of Compression on the Incidence of Symptomatic ETD and MEB: a Phase III Prospective Study.
Official title: The Effect of Rate (Slope) of Compression on the Incidence of Symptomatic Eustachian Tube Dysfunction and Middle Ear Barotrauma: a Phase III Prospective Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ear Barotrauma
Middle Ear Disease
Ear Diseases
Pressure Injury
Eustachian Tube Dysfunction
Middle Ear; Injury
Middle Ear Barotrauma
Keywords: Ear Pressure
Otic Barotrauma
Hyperbaric
Pressure Equalization
O'Neill Grading System
Compression Rate
Lead sponsor: Northwell Health
Sponsor class: OTHER
First posted: 2021-03-18
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: Eustachian tube dysfunction (ETD) and middle ear barotrauma (MEB) are common reported complications during hyperbaric oxygen treatment. The Phase I study data was the first to demonstrate a statistically significant decrease in the occurrence of symptomatic ETD and middle ear barotrauma (MEB). The Phase I Trial suggested the total time interval and rate (slope) of compression (ROC) may be a determining factor in ETD and MEB. This Phase II study investigates an optimal total time interval and rate of compression to reduce ETD and MEB when considering each multiplace treatment (with multiple patients) as the unit of observation collectively as a group, rather than for each individual patient.

Data will be collected prospectively on group patient-treatment exposures. Our investigators randomly assign patient-treatment group exposures to two different rates (slopes) of compression. These are limited to the linear versus the non-linear rates (slopes) of compression identical to two of four compression profiles used in the Phase I and Phase II trials. All patients experiencing symptoms of ETD and MEB requiring compression stops will be evaluated post treatment to confirm the presence of ETD and MEB using the O'Neill Grading System (OGS). Data will be analyzed using the IBM-SPSS statistical software program.

The number of compression holds observed in each of the compression schedules/compression profiles using an identical 15-minute total time interval of compression but varying in the rate (slope) of compression will be recorded as in the Phase I and II studies. Symptomatic patients who required compression stops (as in the Phase I trial) using a USN TT 9 during elective hyperbaric oxygen treatments in a Class A multiplace hyperbaric chamber will be compared. Statistical analysis using descriptive and Inferential statistics will be applied to the patients requiring first stops in the compression profiles. This will be used to further evaluate the data restricted to the rate of compression (linear vs. non-linear) and whether this is associated with the number of compression holds. The 15-minute total time interval of compression will be identical in both compression profiles studied since this was found to be the total time interval of compression with the least number of treatment stops/holds in the phase I and phase II studies.

Detailed description: Eustachian tube dysfunction (ETD) and middle ear barotrauma (MEB) are common reported complications during hyperbaric oxygen treatment. The Phase I study data was the first to demonstrate a statistically significant decrease in the occurrence of symptomatic ETD and middle ear barotrauma (MEB) in specific compression profiles among those used as common standards of care in hyperbaric oxygen treatment. The Phase I Trial suggested the total time interval and rate (slope) of compression (ROC) may be a determining factor in ETD and MEB. The Phase II study investigated tested the robustness of these findings with a larger sample size and failed to determine an optimal rate of compression to reduce ETD and MEB when considering each multiplace treatment (with multiple patients) as the unit of observation collectively as a group, rather than for each individual patient. In this phase III trial we will increase sample size further to determine if the effect size of the rate (slope) of compression is smaller than anticipated in the phase I and II studies requiring a larger sample size and greater power. This study will be restricted to the two compression profiles limited to the 15 minute total time interval of compression which was found to be the time interval associated with the least number of treatment holds or stops.

Data will be collected prospectively on group patient-treatment exposures. The investigators will randomly assign patient-treatment group exposures to a single identical time interval but different rates (slopes) of compression. These compression rates (slopes) were identical to those used in the Phase I and II trials. All patients experiencing symptoms of ETD and MEB requiring compression stops or holds will be evaluated post-treatment to confirm the presence of ETD and MEB using the O'Neill Grading System (OGS) for ETD/MEB.

For approximately 10 years, the investigators hyperbaric center used a routine daily multiplace chamber treatment protocol to a depth of 45 feet of seawater (fsw) (modified U.S. Navy Treatment Table 9). The chamber was compressed over a 10-minute time interval representing a 4.5 fsw/minute uniform rate of compression. This 4.5-fsw/minute compression rate throughout the total 10-minute time interval of treatment was used as a baseline compression rate to compare all other compression schedules \[total compression time interval/compression rates (slopes)\]. The investigators will prospectively collect data on patient-treatment group exposures after formalizing two different compression schedules each including a unique compression rate (slope) linear vs. non-linear but using the same 15-minute time interval of compression. This was similar to the Phase I and Phase II study but limited to two compression profiles.

Data will be collected prospectively on all patients receiving treatment from September 1, 2021, and October 31, 2023, and combined with the data obtained in the Phase I and II trials collected from September 8, 2014 to September 8, 2016; and February 11, 2019, and February 10, 2020 respectively. This Phase III study defines the unit of observations as a multiplace patient-treatment group exposure rather than individual patient treatment exposures. This approach was considered appropriate as a treatment stop or hold in a multiplace chamber affects all other patient occupants in the same treatment group exposure. It results in a hold for all patients in the multiplace chamber during that respective treatment. The possible effects on the other patients in the same treatment group could possibly confound our outcomes. The effect of rate (slope) of compression on an individual patient can be better ascertained at the individual patient level in a monoplace chamber, without influencing the effect on other patients.

To mitigate the risk of confounding, only the first stop will be used as the stop or hold indicator for that particular patient-treatment group exposure. Data will be collected on the patient(s) experiencing the stop or hold. All patients will undergo pre-treatment video otoscopy with baseline tympanic membrane (TM) photos and video of TM motion documenting the patients ability to equalize. This is used to assess potential Eustachian tube patency and proper equalization performance to help exclude individual patient technique as a confounding variable. Photos will be repeated at the end of treatment on any patient(s) complaining of symptoms referable to ETD/MEB that require a stop during compression.

Multiple stops for the same patient on the same treatment will not be considered. Only the first compression stop or hold during each treatment exposure will be recorded or assigned as a patient-treatment stop representing that particular patient-treatment group exposure. Compression stops will be made when any patient experiences difficulty equalizing (requests a stop or complains of ear discomfort of any type).

Repeat video otoscopy will be conducted on all patients complaining of symptoms referable to ETD or MEB to objectively document the grade of barotrauma at the end of the treatment. The O'Neill Grading System will be used to record the severity of the ETD or MEB. The depth of the stop, the treatment number for that particular patient, and the actions taken to alleviate the symptoms during equalization will be recorded.

The depth of the compression stop will be recorded in feet of seawater (fsw) as will be the ascent (fsw) required for the patient to clear the middle ear pressure and relieve the symptoms. The patients symptoms must be resolved, rendering the patient asymptomatic and able to continue the treatment compression profile. All team members (physicians, nurses, and technicians) present and working on the day of the exposure, are responsible for viewing the patients pre and post tympanic membrane photos and determining the grade of barotrauma using the OGS criteria.

All stops were categorized under the respective compression protocol used for that particular patient-treatment group exposure. Data will then compared using both descriptive and inferential statistical analysis including the risk difference, odds ratio (OR), two-tailed Chi Square analysis using α=0.05, and outcomes will be studied separately in a logistic regression analysis.

Eligibility criteria: Inclusion Criteria:

- Any patient meeting the proper diagnosis and indications to be treated with hyperbaric oxygen.

Exclusion Criteria:

* Any patient with absolute contraindications to hyperbaric oxygen treatment
* Patients with chronic bilateral perforation of the tympanic membrane or;
* A history of prior surgical placement of myringotomy tubes.

Primary outcomes:
measure: Hyperbaric oxygen chamber Treatment Stops/Holds during compression
timeFrame: Patients are assessed during each hyperbaric chamber compression until reaching treatment pressure/depth daily throughout the entire treatment course that varies based on diagnosis over 4-12 weeks
measure: Severity of ETD/MEB when a patient has a stop/hold during compression
timeFrame: Patients are assessed during each hyperbaric chamber compression until reaching treatment pressure/depth daily throughout the entire treatment course that varies based on diagnosis over 4-12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Sleepy Hollow
country: United States
facility: Phelps Hospital Northwell Health
state: New York
Study officials:
affiliation: Phelps Hospital Northwell Health
name: Owen J O'Neill, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Phelps Hospital Northwell Health
name: David Dayya, DO, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
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