Efficacy of Percussive Ventilation Therapy (MetaNeb ®) Compared With Mucolytic Agents for Atelectasis in the Mechanically Ventilated Pediatric Patient

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02168387
• Collaborator: (none)
• Enrollment: 39
• Arms: 2
• Duration (Months): 19

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate whether a therapy that uses a machine called a continuous high frequency oscillator (CHFO) is more successful at removing mucus than medications that thin out the mucus.

Condition or Disease	Intervention/Treatment	Phase
Atelectasis	Device: continuous high frequency oscillator (CHFO); Drug: Acetylcysteine; Drug: dornase alfa	Phase 4

Detailed Description

Both of these therapies (CHFO and medication) are currently used in the Pediatric Intensive Care Unit and Pediatric Cardiac Intensive Care Unit. This research study is being done because the investigator is trying to learn if the mechanical removal of mucus with CHFO will effectively re-inflate the collapsed area of lung. Specifically, the study team will determine if CHFO can improve lung inflation with the same or improved vital signs (heart rate, blood pressure, and breathing rate), and the same or improved ability to help the lungs move oxygen into the blood.

One of the problems with the medication approach is that while it thins out the mucus, actual removal from the lung requires a strong cough which is difficult for infants and children to produce when they are sedated and on a ventilator (breathing machine).

Thus, the aim of this research study is to test whether children with atelectasis on a ventilator are more likely to improve with mechanical removal of their mucus with the CHFO as compared with medications that thin out the mucus. CHFO and all the medications used in this study are part of the standard of care for atelectesis. However, there is no information on which combination works best and no one agrees that one approach is more effective than another. Usually patients are evaluated for 48 hours after starting treatment, before adding or making any changes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy of Percussive Ventilation Therapy (MetaNeb ®) Compared With Mucolytic Agents for Atelectasis in the Mechanically Ventilated Pediatric Patient
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: continuous high frequency oscillator (CHFO) Subjects randomized to receive therapy with the CHFO will receive a 20 minute treatment every 6 hours for 48 hours.	Device: continuous high frequency oscillator (CHFO)
Active Comparator: medication Subjects randomized to receive the medications will receive acetylcysteine and dornase alfa, two medications frequently used in the treatment of atelectasis. The medications will alternate every 6 hours for 48 hours.	Drug: Acetylcysteine; Drug: dornase alfa

Outcome Measures

Primary Outcome Measures

1. Improvement of Atelectasis [after 48 hours of therapy]

   An atelectasis score (AS), as published by Deakins, et al. 2002, was assigned to each radiograph as follows: 0 Complete resolution of collapse Partial collapse of 1 segment or lobe Partial collapse of ≥ 2 segments or lobes Complete collapse of 1 segment or lobe Complete collapse of ≥ 2 segments or lobes In the event of inter-rater disagreement, the scores were averaged. Improvement was defined as any decrease in AS ≥ 0.5. Worsening was defined as an increase in AS ≥ 0.5 or escalation of respiratory support modality (i.e. high frequency ventilation).

Secondary Outcome Measures

1. Change in Capnography (Vd/Vt) [baseline and 48 hours]

   The deadspace-to-tidal volume (Vd/Vt) ratio is a parameter that is measured in mechanically ventilated patients as a way to assess the severity of gas exchange impairment and to assist in determining whether a patient is ready to be weaned from the ventilator. The change from baseline was measured at 48 hours, with a decreasing ratio indicating improvement.

2. Change in Quantity and Quality of Suctioned Mucus [baseline and 48 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Informed consent from parent or legal guardian.

2. Age < 18 years and admitted to the PICU or PCICU.

3. Conventionally ventilated.

4. Mucolytics are being initiated by clinical team for treatment of atelectasis.

5. Endotracheal tube ≥ 3.5 mm internal diameter.

Exclusion Criteria:

1. Receiving chronic mucolytic or continuous high frequency oscillation therapy.

2. Clinically significant pleural effusion.

3. Status post cardiothoracic surgery with open chest.

4. Pneumothorax.

5. Pulmonary hemorrhage.

6. Escalating doses of vasoactive agents (i.e. dopamine or epinephrine).

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Ira Cheifetz, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02168387
• Other Study ID Numbers: Pro00026503
• First Posted: Jun 20, 2014
• Last Update Posted: Mar 3, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by Duke University: atelectasis; continuous high frequency oscillator; acetylcysteine; dornase alfa
• Additional relevant MeSH terms: Pulmonary Atelectasis; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Recruitment Details	All mechanically ventilated patients 0-17 years of age admitted to the Pediatric Intensive Care Unit (PICU) and Pediatric Cardiac Intensive Care Unit (PCICU) from January 2011 to March 2012 with radiographic evidence of atelectasis for which mucolytics or CHFO therapy were being initiated by the patient care team were screened for enrollment.

Arm/Group Title	Medication	Continuous High Frequency Oscillator (CHFO)
Arm/Group Description	Subjects randomized to receive the medications will receive acetylcysteine and dornase alfa, two medications frequently used in the treatment of atelectasis. The medications will alternate every 6 hours for 48 hours. Acetylcysteine dornase alfa	Subjects randomized to receive therapy with the CHFO will receive a 20 minute treatment every 6 hours for 48 hours. continuous high frequency oscillator (CHFO)
Period Title: Overall Study
STARTED	20	19
COMPLETED	13	16
NOT COMPLETED	7	3

Baseline Characteristics

Arm/Group Title	Medication	Continuous High Frequency Oscillator (CHFO)	Total
Arm/Group Description	Subjects randomized to receive the medications will receive acetylcysteine and dornase alfa, two medications frequently used in the treatment of atelectasis. The medications will alternate every 6 hours for 48 hours.	Subjects randomized to receive therapy with the CHFO will receive a 20 minute treatment every 6 hours for 48 hours.	Total of all reporting groups
Overall Participants	20	19	39
Age, Customized (participants) [Number]
less than or equal to 1 year	11 55%	10 52.6%	21 53.8%
greater than 1 year	9 45%	9 47.4%	18 46.2%
Sex: Female, Male (Count of Participants)
Female	11 55%	8 42.1%	19 48.7%
Male	9 45%	11 57.9%	20 51.3%
Region of Enrollment (participants) [Number]
United States	20 100%	19 100%	39 100%

Outcome Measures

1. Primary Outcome

Title	Improvement of Atelectasis
Description	An atelectasis score (AS), as published by Deakins, et al. 2002, was assigned to each radiograph as follows: 0 Complete resolution of collapse Partial collapse of 1 segment or lobe Partial collapse of ≥ 2 segments or lobes Complete collapse of 1 segment or lobe Complete collapse of ≥ 2 segments or lobes In the event of inter-rater disagreement, the scores were averaged. Improvement was defined as any decrease in AS ≥ 0.5. Worsening was defined as an increase in AS ≥ 0.5 or escalation of respiratory support modality (i.e. high frequency ventilation).
Time Frame	after 48 hours of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medication	Continuous High Frequency Oscillator (CHFO)
Arm/Group Description	Subjects randomized to receive the medications will receive acetylcysteine and dornase alfa, two medications frequently used in the treatment of atelectasis. The medications will alternate every 6 hours for 48 hours.	Subjects randomized to receive therapy with the CHFO will receive a 20 minute treatment every 6 hours for 48 hours.
Measure Participants	13	16
Improved in 48 h	6 30%	7 36.8%
Worse in 48 hr	3 15%	6 31.6%
No change in 48 hr	4 20%	3 15.8%

2. Secondary Outcome

Title	Change in Capnography (Vd/Vt)
Description	The deadspace-to-tidal volume (Vd/Vt) ratio is a parameter that is measured in mechanically ventilated patients as a way to assess the severity of gas exchange impairment and to assist in determining whether a patient is ready to be weaned from the ventilator. The change from baseline was measured at 48 hours, with a decreasing ratio indicating improvement.
Time Frame	baseline and 48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medication	Continuous High Frequency Oscillator (CHFO)
Arm/Group Description	Subjects randomized to receive the medications will receive acetylcysteine and dornase alfa, two medications frequently used in the treatment of atelectasis. The medications will alternate every 6 hours for 48 hours.	Subjects randomized to receive therapy with the CHFO will receive a 20 minute treatment every 6 hours for 48 hours.
Measure Participants	13	16
Mean (Standard Deviation) [ratio]	-0.04 (0.08)	0.03 (0.09)

3. Secondary Outcome

Title	Change in Quantity and Quality of Suctioned Mucus
Time Frame	baseline and 48 hours

Outcome Measure Data

Analysis Population Description

These data were not obtained due to technical difficulties.

Arm/Group Title	Medication	Continuous High Frequency Oscillator (CHFO)
Arm/Group Description	Subjects randomized to receive the medications will receive acetylcysteine and dornase alfa, two medications frequently used in the treatment of atelectasis. The medications will alternate every 6 hours for 48 hours.	Subjects randomized to receive therapy with the CHFO will receive a 20 minute treatment every 6 hours for 48 hours.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Medication		Continuous High Frequency Oscillator (CHFO)
Arm/Group Description	Subjects randomized to receive the medications will receive acetylcysteine and dornase alfa, two medications frequently used in the treatment of atelectasis. The medications will alternate every 6 hours for 48 hours.		Subjects randomized to receive therapy with the CHFO will receive a 20 minute treatment every 6 hours for 48 hours.
All Cause Mortality
	Medication		Continuous High Frequency Oscillator (CHFO)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Medication		Continuous High Frequency Oscillator (CHFO)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		0/19 (0%)
General disorders
death due to underlying disease	1/20 (5%)	1	0/19 (0%)	0
Other (Not Including Serious) Adverse Events
	Medication		Continuous High Frequency Oscillator (CHFO)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/19 (0%)

Limitations/Caveats

Small sample size in a single center study. Children who were extubated prior to the end of the study were not accounted for, as this was not a primary endpoint.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.