Evaluating the Utility of Continuous Positive Airway Pressure in the Treatment of High Altitude Pulmonary Edema

Multicenter Randomized Double-Blind Control Trial Evaluating the Utility of Continuous Positive Airway Pressure (CPAP) in the Treatment of High Altitude Pulmonary Edema (HAPE)

The primary objective is to evaluate the efficacy of continuous positive pressure on resolution of high-altitude pulmonary edema vs high flow oxygen. The secondary objective is to derive an incidence of high-altitude pulmonary edema based on the elevation and timing from which the subject arrives. Additionally, in a convenience sample of the base study population, an ultrasound evaluation for the presence of B lines in the lungs will be conducted after 2 hours.

Study Overview

• Status: Completed
• Conditions: Continuous Positive Airway Pressure; High Altitude Pulmonary Edema
• Intervention / Treatment: Device: CPAP mask system; Drug: Nifedipine 30 MG; Device: CPAP mask system without PEEP

Detailed Description

Multicenter, double-blinded, randomized control trial. Enrollment is based on presentation to one of the treating facilities with clinical signs and symptoms of high-altitude pulmonary edema with a recent arrival at high altitude, an oxygen saturation below 85%, and radiographic evidence of noncardiogenic pulmonary edema. A total of 264 patients will be randomized 1:1 across 2 study arms: a CPAP mask set to 15cm H2O and an altered CPAP mask in which the pressure valve has been modified to deliver no positive pressure. All patients will be treated with 30mg nifedipine XR. Except for the application of positive pressure, all other interventions are performed in the context of everyday clinical practice, and thus will be equivalent for participants in both arms. Patients will be evaluated every 30 minutes for their ability to maintain an oxygen saturation of 92% with a normal respiratory rate and no signs of increased work of breathing on 2 liters of nasal cannula oxygen for a total of up to a maximum treatment length of 2 hours. The primary efficacy endpoint will be assessed every 30 minutes for 2 hours.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Breckenridge, Colorado, United States, 80424
      • Breckenridge Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female, age 18 years or greater
• Oxygen saturation below 85%
• Recent arrival to high altitude
• Dyspnea and cough
• Xray revealing non-cardiogenic pulmonary edema

Exclusion Criteria:

• Pregnancy
• Age below 18
• Patients with respiratory failure requiring intubation
• Patients with altered mental status
• Patients with impaired decision-making capacity
• Patients with a history of congestive heart failure, CAD, COPD, asthma, known current pneumonia
• Extreme facial hair precluding application of CPAP

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: CPAP; Participants will be treated with CPAP. All patients will be treated with nifedipine unless there is a contraindication like hypotension and bradycardia.	Device: CPAP mask system; Intervention group will receive 15cm of H2O of positive end expiratory pressure; Drug: Nifedipine 30 MG; All participants will receive this intervention
Placebo Comparator: Control: High flow oxygen; Participants will be treated with an altered CPAP mask that will deliver high flow oxygen. All patients will be treated with nifedipine unless there is a contraindication like hypotension and bradycardia.	Drug: Nifedipine 30 MG; All participants will receive this intervention; Device: CPAP mask system without PEEP; Placebo group will receive high flow oxygen via altered CPAP mask system without providing any positive end expiratory pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to resolution of HAPE	The amount of time it took to maintain oxygen saturation over 92% on 2L NC oxygen	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence or absence of ultrasound detectable B lines	A convenience sample of the total study population will have a bedside pulmonary ultrasound at time zero and two hours	2 hours
Characterization of time at altitude to development of HAPE	A descriptive measurement of the time since the patient arrived at altitude until the development of HAPE	2 hours
Incidence of HAPE by native altitude and reported sleeping altitude	Data will be collected and analyzed to seek a relationship between the subjects home altitude and the altitude of their sleep while at high altitude	2 hours

Collaborators and Investigators

• Sponsor: Centura Health
• Collaborators: Pulmodyne, Inc.
• Investigators: Principal Investigator: Todd Bolotin, MD, Centura Health

Publications and helpful links

General Publications

• Basnyat B, Murdoch DR. High-altitude illness. Lancet. 2003 Jun 7;361(9373):1967-74. doi: 10.1016/S0140-6736(03)13591-X.
• Murdoch DR. Prevention and Treatment of High-altitude Illness in Travelers. Curr Infect Dis Rep. 2004 Feb;6(1):43-49. doi: 10.1007/s11908-004-0023-4.
• Gonzalez Garay A, Molano Franco D, Nieto Estrada VH, Marti-Carvajal AJ, Arevalo-Rodriguez I. Interventions for preventing high altitude illness: Part 2. Less commonly-used drugs. Cochrane Database Syst Rev. 2018 Mar 12;3(3):CD012983. doi: 10.1002/14651858.CD012983.
• Gallagher SA, Hackett PH. High-altitude illness. Emerg Med Clin North Am. 2004 May;22(2):329-55, viii. doi: 10.1016/j.emc.2004.02.001.
• Nieto Estrada VH, Molano Franco D, Medina RD, Gonzalez Garay AG, Marti-Carvajal AJ, Arevalo-Rodriguez I. Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs. Cochrane Database Syst Rev. 2017 Jun 27;6(6):CD009761. doi: 10.1002/14651858.CD009761.pub2.
• Stoltzfus S. The role of noninvasive ventilation: CPAP and BiPAP in the treatment of congestive heart failure. Dimens Crit Care Nurs. 2006 Mar-Apr;25(2):66-70. doi: 10.1097/00003465-200603000-00006.
• Luks AM, Auerbach PS, Freer L, Grissom CK, Keyes LE, McIntosh SE, Rodway GW, Schoene RB, Zafren K, Hackett PH. Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2019 Update. Wilderness Environ Med. 2019 Dec;30(4S):S3-S18. doi: 10.1016/j.wem.2019.04.006. Epub 2019 Jun 24.
• Johnson PL, Johnson CC, Poudyal P, Regmi N, Walmsley MA, Basnyat B. Continuous positive airway pressure treatment for acute mountain sickness at 4240 m in the Nepal Himalaya. High Alt Med Biol. 2013 Sep;14(3):230-3. doi: 10.1089/ham.2013.1015.
• Hebert PC, Stanbrook M. Indication creep: physician beware. CMAJ. 2007 Sep 25;177(7):697, 699. doi: 10.1503/cmaj.071223. Epub 2007 Sep 5. No abstract available.
• Walmsley M. Continuous positive airway pressure as adjunct treatment of acute altitude illness. High Alt Med Biol. 2013 Dec;14(4):405-7. doi: 10.1089/ham.2013.1059.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Actual): September 13, 2023
• Study Completion (Actual): September 13, 2023

Study Registration Dates

• First Submitted: December 1, 2019
• First Submitted That Met QC Criteria: December 3, 2019
• First Posted (Actual): December 5, 2019

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Hypertension; Altitude Sickness; Hypertension, Pulmonary; Edema; Pulmonary Edema; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Nifedipine
• Other Study ID Numbers: 1389613

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes