Effect of Rate (Slope) of Compression on the Incidence of Symptomatic ETD and MEB: a Phase III Prospective Study.

Pressure Injury Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04804098
• Other study ID #: Compression Hyperbaric III
• Status: Recruiting
• Phase: N/A
• Start date: September 20, 2021
• Est. completion date: December 1, 2024

Study information

• Verified date: October 2023
• Source: Northwell Health
• Contact: Owen J O'Neill, MD, MPH
• Phone: 914-366-6665
• Email: ooneill[@]northwell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 1, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Barotrauma
• Crush Injuries
• Ear Barotrauma
• Ear Diseases
• Eustachian Tube Dysfunction
• Middle Ear Barotrauma
• Middle Ear Disease
• Middle Ear; Injury
• Pressure Injury
• Wounds and Injuries

Intervention

Procedure:
• Compression Profile/Schedule: 15 minute Non-Linear compression from start of the daily treatment until treatment pressure is reached (45 fsw)
Patients will be compressed according to the 15 minute non-linear compression schedule on a rotating daily basis. A total of 2 randomized hyperbaric treatment compression profiles (accepted standards of care) will be alternated over the patients course of treatment on a daily basis daily to the prescribed treatment depth. There are multiple patients exposed during the compression profile randomized for that day. The patients are exposed over the course of 4-12 weeks using one of the two compression protocols to be studied on alternating days.
• Compression Profile/Schedule: 15 minute Linear compression from start of the daily treatment until treatment pressure is reached (45 fsw)
Patients will be compressed according to the 15 minute linear compression schedule on a rotating daily basis with compression. A total of 2 randomized hyperbaric treatment compression profiles (accepted standards of care) will be alternated over the patients course of treatment on a daily basis daily to the prescribed treatment depth. There are multiple patients exposed during the compression profile randomized for that day. The patients are exposed over the course of 4-12 weeks using one of the two compression protocols to be studied on alternating days.

Locations

Country	Name	City	State
United States	Phelps Hospital Northwell Health	Sleepy Hollow	New York

Sponsors (1)

Lead Sponsor	Collaborator
Northwell Health

Country where clinical trial is conducted

United States, 

References & Publications (17)

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Camporesi EM. Side effects of hyperbaric oxygen therapy. Undersea Hyperb Med. 2014 May-Jun;41(3):253-7. — View Citation

Fitzpatrick DT, Franck BA, Mason KT, Shannon SG. Risk factors for symptomatic otic and sinus barotrauma in a multiplace hyperbaric chamber. Undersea Hyperb Med. 1999 Winter;26(4):243-7. — View Citation

Goplen FK, Gronning M, Aasen T, Nordahl SH. Vestibular effects of diving - a 6-year prospective study. Occup Med (Lond). 2010 Jan;60(1):43-8. doi: 10.1093/occmed/kqp148. Epub 2009 Oct 23. — View Citation

Hadanny A, Meir O, Bechor Y, Fishlev G, Bergan J, Efrati S. Seizures during hyperbaric oxygen therapy: retrospective analysis of 62,614 treatment sessions. Undersea Hyperb Med. 2016 Jan-Feb;43(1):21-8. — View Citation

Heyboer M 3rd, Wojcik SM, Grant WD, Chambers P, Jennings S, Adcock P. Middle ear barotrauma in hyperbaric oxygen therapy. Undersea Hyperb Med. 2014 Sep-Oct;41(5):393-7. — View Citation

Lima MA, Farage L, Cury MC, Bahamad F Junior. Update on middle ear barotrauma after hyperbaric oxygen therapy-insights on pathophysiology. Int Arch Otorhinolaryngol. 2014 Apr;18(2):204-9. doi: 10.1055/s-0034-1366974. Epub 2014 Feb 10. — View Citation

Mozdzanowski C, Perdrizet GA. Peripheral neuropathy may increase the risk for asymptomatic otic barotrauma during hyperbaric oxygen therapy: research report. Undersea Hyperb Med. 2014 Jul-Aug;41(4):267-72. — View Citation

Nasole E, Zanon V, Marcolin P, Bosco G. Middle ear barotrauma during hyperbaric oxygen therapy; a review of occurrences in 5,962 patients. Undersea Hyperb Med. 2019 Mar-Apr-May;46(2):101-106. — View Citation

Ng AWA, Muller R, Orton J. Incidence of middle ear barotrauma in staged versus linear chamber compression during hyperbaric oxygen therapy: a double blinded, randomized controlled trial. Undersea Hyperb Med. 2017 Mar-Apr;44(2):101-107. doi: 10.22462/3.4.2017.3. — View Citation

O'Neill OJ, Weitzner ED. The O'Neill grading system for evaluation of the tympanic membrane: A practical approach for clinical hyperbaric patients. Undersea Hyperb Med. 2015 May-Jun;42(3):265-71. — View Citation

Plafki C, Peters P, Almeling M, Welslau W, Busch R. Complications and side effects of hyperbaric oxygen therapy. Aviat Space Environ Med. 2000 Feb;71(2):119-24. — View Citation

Sanders RW. Controlling the rate of middle ear barotrauma: an editorial perspective. Undersea Hyperb Med. 2014 Sep-Oct;41(5):355-6. No abstract available. — View Citation

Toklu AS, Shupak A, Yildiz S, Aktas S, Ertracht O, Ay H, Adir Y, Cimsit M. Aural barotrauma in submarine escape: is mastoid pneumatization of significance? Laryngoscope. 2005 Jul;115(7):1305-9. doi: 10.1097/01.MLG.0000165804.09586.B6. — View Citation

Vahidova D, Sen P, Papesch M, Zein-Sanchez MP, Mueller PH. Does the slow compression technique of hyperbaric oxygen therapy decrease the incidence of middle-ear barotrauma? J Laryngol Otol. 2006 Jun;120(6):446-9. doi: 10.1017/S002221510600079X. — View Citation

Varughese L, O'Neill OJ, Marker J, Smykowski E, Dayya D. The effect of compression rate and slope on the incidence of symptomatic Eustachian tube dysfunction leading to middle ear barotrauma: a Phase I prospective study. Undersea Hyperb Med. 2019 Mar-Apr-May;46(2):95-100. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hyperbaric oxygen chamber Treatment Stops/Holds during compression	Hyperbaric oxygen treatment (HBOT) protocols include a compression phase. Pressure is increased until final treatment pressure is achieved. Pressure changes vary between 14.7 psi to 35 psi. Patients experience symptoms of pain or pressure in the middle ear space because they cannot clear middle ear pressure upon compression of the chamber. Pressure symptoms are time related but not as yet slope related. Using varying rates of pressure may decrease discomfort related to clearing middle ear pressure known as Eustachian tube dysfunction (ETD) and middle ear barotrauma (MEB). They are the most common adverse effects of HBOT. The authors believe a change in slope rate of compression may decrease the occurrence of stops and decrease the incidence of ETD and MEB during HBOT. Decreasing rate of compression may further mitigate risk and decrease the incidence of symptomatic ETD and MEB.	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
Primary	Severity of ETD/MEB when a patient has a stop/hold during compression	Photo otoscopy and the severity of eustachian tub dysfunction and/or middle ear barotrauma will be defined using the O'Neill Grading System when a patient experiences a stop or hold during the compression phase of hyperbaric oxygen treatment.; O'Neill Grading System: 0 = Symptoms of Eustachian tube dysfunction with no objective signs of barotrauma on otoscopy; = Objective evidence indicating the presence of erythema, air trapping or serous/serosanguinous effusion; = Any frank bleeding in the middle ear space, tympanic membrane, external ear canal, or perforation	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