PEP Flute-selfcare in COVID-19 (PEP-CoV)

PEP Flute-selfcare to Prevent Respiratory Deterioration and Hospitalization Among COVID-19 Patients: a Randomized Trial

Most research on the coronavirus SARS-CoV-2 and COVID-19 disease relate to screening measures, development of vaccines and optimising treatment of hospitalised patients. It is likely that this pandemic will be ongoing for several years until a high level of immunity is reached in the population or a vaccine has been developed. Thus, there is a need of measures to help the SARS-CoV-2 infected individual at home to overcome the course of disease with less symptoms and strain. A Positive Expiratory Pressure (PEP) flute is feasible for home use and it is possible that regular use of PEP flute may prevent the progression of respiratory symptoms in non-hospitalized individuals with COVID-19 disease.

The primary objective of the study is to examine the effect of PEP flute use among SARS-CoV-2 infected, non-hospitalized patients on self-reported change in COPD Assessment Test (CAT) score during 30 days of follow-up.

The secondary objectives are to compare the development in hospitalization rates and use of antibiotics in the intervention group and the control group during the follow-up period.

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2
• Intervention / Treatment: Device: PEP flute

Detailed Description

It is hypothesized that the PEP flute has positive effects on SARS-CoV-2 infected individual's self-reported respiratory symptoms such as dyspnoea, coughing and perceived mucus clearance through beneficial effects on lung function and airway clearance. Furthermore, the investigators expect a lower rate of hospitalization and use of antibiotics in the intervention group as compared to the control group.

Finally, potential subgroup effects by gender, age, comorbidity and BMI at study entry will be explored for all outcomes.

Based upon a sample size estimation the investigators assess that inclusion of 200 participants in each intervention arm will be an adequate number. Based on the present testing strategy and COVID-19 incidence, current expectations are that two months should be enough to recruit 400 patients. The investigators will allow for recruitment to the end of December 2020, but will terminate enrolment at n = 400.

Link to detailed protocol paper will be added once published.

• Study Type: Interventional
• Enrollment (Actual): 378
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Frederiksberg, Denmark, 2000
    • Research Unit for Dietary Studies at the Parker Institute, Bispebjerg and Frederiksberg Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Positive SARS-CoV-2
• Symptoms of SARS-CoV-2 infection e.g. fever, cough and shortness of breath.
• Access to use a smartphone
• Can reply to a questionnaire (sent on email, text messages or via telephone interview) in Danish
• Given informed consent

Exclusion Criteria:

• Age < 18 years.
• Any condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or which obstruct participation, such as psychiatric disorders.
• Hospitalised patients or citizens living in nursing homes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; The participants will be handed three airway resistances equivalent to a resistance of 10-20 cm H2O alongside one PEP flute. Two videos will guide the participants in use of the PEP flute; one with instructions of the rationale and how to use the flute, including how to choose the suitable resistance and one video, which gives instructions of hygienic maintenance. Participants in the intervention group will be advised to continue use of their PEP flute in the active intervention period of 30 days or at least if they still have respiratory symptoms. They will receive daily text-messages to prompt their reporting and to use the PEP flute according to instructions.	Device: PEP flute; Participants are advised to use a PEP flute at least three times daily at an appropriate resistance. Ideally, each session consists of 15 breaths (for approximately 1 minute) repeated twice at an upright position.
No Intervention: Control group; The participants in the control group will receive daily text-messages to prompt their reporting of CAT-scores. To avoid attrition of the trial due to early recovery of symptoms, the project manager will call the participants by phone at day 15 to ask them about their present condition (i.e. CAT-score) and address potential concerns of continued participation of the trial. Otherwise, they will only receive usual care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-reported CAT-score (COPD Assessment Test)	CAT-scores will be measured using a telephone administered questionnaire. The CAT-score is validated to evaluate symptoms in COPD patients. Eight items covers symptoms of cough, sputum, chest pain, dyspnoea, activities of daily living at home, feeling safe at home despite symptoms (modified for the present study from feeling safe at leaving home despite symptoms), sleep quality and vigour. The eight items sum up to a range of 0-40 with higher scores indicating more respiratory impairment. Although validated for COPD-use, the CAT-scale is considered useful in the present study because several of the items (dyspnoea, cough, fatigue, sputum and pleuritic chest pain) previously have been used as outcome variables in pneumonia studies. The outcome assessment can be taken within + 1 week for the scheduled visit.	Day 30.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital admissions	Will be obtained from the Danish National Patient Registry, from which also data of comorbidity will be retrieved.	Up to day 30, 90 and 180.
Use of antibiotics	Will be obtained from the Danish National Prescription Registry.	Up to day 30, 90 and 180.
Self-reported CAT-score (COPD Assessment Test)	CAT-scores will be measured using a telephone or email-administered questionnaire. The outcome assessment can be taken within + 1 week for the scheduled visit.	Day 90, Day 180.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious Adverse Events	Assessed by Common Terminology Criteria for Adverse Event (CTCAE).	During treatment, up to 30 days.
General and respiratory symptoms	Measured according to the COVIDmeter from Statens Serum Institut using a telephone or email-administered questionnaire. The outcome assessment can be taken within + 1 week for the scheduled visit.	Day 30, 90, Day 180.

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital
• Collaborators: Hvidovre University Hospital
• Investigators: Principal Investigator: Berit L. Heitmann, Professor, Ph.D, Research Unit for Dietary Studies at the Parker Institute, Bispebjerg and Frederiksberg Hospitals, Denmark

Publications and helpful links

General Publications

• Mollerup A, Henriksen M, Larsen SC, Bennetzen AS, Simonsen MK, Kofod LM, Knudsen JD, Nielsen XC, Weis N, Heitmann BL. Effect of PEP flute self-care versus usual care in early covid-19: non-drug, open label, randomised controlled trial in a Danish community setting. BMJ. 2021 Nov 24;375:e066952. doi: 10.1136/bmj-2021-066952.
• Mollerup A, Larsen SC, Bennetzen AS, Henriksen M, Simonsen MK, Weis N, Kofod LM, Heitmann BL. PEP-CoV protocol: a PEP flute-self-care randomised controlled trial to prevent respiratory deterioration and hospitalisation in early COVID-19. BMJ Open. 2021 Jun 30;11(6):e050582. doi: 10.1136/bmjopen-2021-050582.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2020
• Primary Completion (Actual): March 29, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Airway clearance techniques; Respiratory symptoms; Positive expiratory pressure; Positive expiratory pressure flute
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 0211-00023B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No