Pseudoephedrine Prophylaxis for Prevention of Middle Ear Barotrauma in Hyperbaric Oxygen Therapy

NCT04332211 — Phase 4, Completed, 105 participants, University of Maryland, Baltimore

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Registry	NCT04332211
Status	Completed
Phase	Phase 4
Study type	Interventional; randomized, parallel, masking: quadruple, prevention
Enrollment	105 (Actual)
Sponsor	University of Maryland, Baltimore (Other)
Conditions	Barotrauma;Ear
Interventions	Hyperbaric Oxygen Therapy, Pseudoephedrine 60 MG, Placebo oral tablet (Procedure, drug)
Dates	start 2021-05-01, primary completion 2023-07-12, completion 2023-07-12, first posted 2020-04-02, last updated 2025-01-08
Locations	1 site in United States

-Summary

Hyperbaric oxygen therapy (HBOT) utilizes 100% oxygen delivery at a pressure greater than 1 atm for the treatment of various emergent medical conditions including carbon monoxide poisoning. The most commonly associated complication of HBOT is middle ear barotrauma (MEB) which occurs when the eustachian tube does not allow air to enter the middle ear space to equalize the pressure between the ambient environment and the inner ear. Patients experiencing MEB usually feel pressure or pain in their ear(s). The spectrum of symptoms ranges from sensation of ear fullness and muffled hearing to severe pain, vertigo and tympanic membrane rupture. The incidence of MEB, depending on the definition used is between 2-45%. The severe discomfort associated with MEB sometimes causes HBOT to be postponed or abandoned. Last year 27/991 treatments at our Center for Hyperbaric and Dive Medicine were aborted due to MEB. Currently there is no objective criteria for predicting which patients will experience these complications, nor is there consensus on effective prevention measures. At our facility, oxymetazoline, a topical nasal decongestant, is the standard rescue medication administered for patients that have symptoms of MEB during HBOT. This is despite two negative studies showing that this medication does not work any better than placebo. Other studies involving scuba divers and airplane travelers showed that oral pseudoephedrine is effective in decreasing MEB. However, the use of pseudoephedrine for patients undergoing HBOT has not been studied. The investigators plan to perform a randomized double blind placebo control trial to determine if pseudoephedrine is effective in decreasing the rate of MEB during HBOT.

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+Detailed description

Aim 1: To investigate the efficacy of pre-treatment with oral pseudoephedrine 60mg for decreasing MEB during HBOT.

Hypothesis: Patients randomized to pseudoephedrine will have a lesser need for oxymetazoline rescue therapy while being compressed. They will also report less ear pain once at pressure compared to patients receiving placebo.

Aim 2: To measure the incidence of MEB during HBOT. The investigators will also identify factors (age, gender, medical history) that could predispose an individual to developing MEB during HBOT.

Hypothesis: The incidence of MEB defined as requiring stopping compression of the chamber and oxymetazoline rescue will be greater than 30%. Female sex, age above 60, and prior history of ear conditions will be associated with development of MEB.

+Arms and interventions

Arm	Type	Interventions	Description
Pseudoephedrine Group	Experimental	Procedure: Hyperbaric Oxygen Therapy; Drug: Pseudoephedrine 60 MG	Patients randomized to pseudoephedrine prior to hyperbaric therapy
Placebo Group	Placebo comparator	Procedure: Hyperbaric Oxygen Therapy; Drug: Placebo oral tablet	Patients randomized to placebo prior to hyperbaric therapy

Hyperbaric Oxygen Therapy (Procedure): Hyperbaric oxygen therapy (HBOT) utilizes 100% oxygen delivery at a pressure greater than 1 atmosphere for the treatment of various emergent medical conditions.
Pseudoephedrine 60 MG (Drug): administer either pseudoephedrine or placebo orally to patients requiring hyperbaric oxygen therapy
Placebo oral tablet (Drug): administer either pseudoephedrine or placebo orally to patients requiring hyperbaric oxygen therapy

+Outcome measures

Primary outcomes

Requirement of Oxymetalozine Rescue for Ear Pain During Hyperbaric Therapy Compression [12 minutes]: middle ear barotrauma will be sensed as pain and inability to "clear" the ear to pressure during chamber pressurization. If the patient requires rescue oxymetazoline nasal spray therapy (usual care) they will be counted as having developed middle ear barotrauma.

Secondary outcomes

Middle Ear Barotrauma Documentation Based on Otoscopy [1 minute]: visual inspection of the tympanic membrane after completion of hyperbaric oxygen therapy by the attending physician and classification based on the Teed score. We are only measuring no injury versus any injury.
Patient Description of Ear Pain [1 minute]: Patients will be asked to provide a numerical scale level of pain before and after hyperbaric therapy. The scale is from 0 to 10. We only are interested in no pain versus presence of any pain.

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* New patient requiring HBOT (either inpatient or outpatient)
* Age greater than or equal to 18 years and less than 80 years
* Fluent in English
* Full decision capacity
* Able and medically cleared to swallow a pill

Exclusion Criteria:

* Contraindication to pseudoephedrine (MAOI use, pregnancy, glaucoma, heart disease, allergy to drug class)
* SBP >160
* DBP > 90
* HR >100
* Decongestant/antihistamine/pseudoephedrine/nasal steroid/oxymetazoline use within 12 hours.
* Prisoner
* Intubated
* Unable take PO meds

+Posted results

Participant flow

Milestone	Pseudoephedrine Group	Placebo Group
Started	40	41
Completed	40	41
Not completed	0	0

Outcome results

Requirement of Oxymetalozine Rescue for Ear Pain During Hyperbaric Therapy Compression (Primary), Count of participants, Participants: Pseudoephedrine Group 8; Placebo Group 11
Middle Ear Barotrauma Documentation Based on Otoscopy (Secondary), Count of participants, Participants: Pseudoephedrine Group 6; Placebo Group 11
Patient Description of Ear Pain (Secondary), Count of participants, Participants: Pseudoephedrine Group 5; Placebo Group 12

Adverse events

Time frame: 4 hours

Arm	Deaths	Serious adverse events	Other adverse events
Pseudoephedrine Group	0/40 (0.0%)	0/40 (0.0%)	0/40 (0.0%)
Placebo Group	0/41 (0.0%)	0/41 (0.0%)	0/41 (0.0%)

+Locations (1)

Facility	City	Country	Status
University of Maryland Medical Center	Baltimore, Maryland	United States

+Study documents

Study Protocol and Statistical Analysis Plan (PDF, 2022-01-17)
Informed Consent Form (PDF, 2023-03-30)

+Investigators

Siamak Moayedi, MD, Principal investigator, University of Maryland School of Medicine, Department of Emergency Medicine