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A Randomized Trial of Outpatient Oxygen Weaning Strategies in Premature Infants

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ClinicalTrials.gov Identifier: NCT01994954
Recruitment Status : Completed
First Posted : November 26, 2013
Results First Posted : October 2, 2019
Last Update Posted : October 2, 2019
Sponsor:
Collaborators:
Bay State Medical Center
UConn Health
University of Vermont Medical Center
Connecticut Children's Medical Center
Patient-Centered Outcomes Research Institute
University of Kentucky
Boston Children's Hospital
Dartmouth-Hitchcock Medical Center
Tufts Medical Center
Westchester Medical Center
Information provided by (Responsible Party):
Lawrence Rhein, University of Massachusetts, Worcester

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Diagnostic
Condition Premature Infants
Intervention Other: RHO
Enrollment 196
Recruitment Details Eligible patients were screened from November 2013 to December 2017. Subjects were screened either before NICU discharge with anticipation of HOT therapy or at their first pulmonary clinic visit. Each subject was consented at their first outpatient pulmonary clinic or NICU follow-up clinic with a pulmonary component.
Pre-assignment Details  
Arm/Group Title Arm A:Standard Therapy Arm B:RHO
Hide Arm/Group Description Infants' oxygen will be increased, decreased, or maintained based on brief structured assessments during monthly clinic visits. Polysomnograms will be utilized prior to final discontinuation of oxygen. RHO will only be utilized on the night prior to and during the polysomnogram to compare these two modalities.

Infants will have the same monthly clinic assessments as in Arm A, but also will utilize RHO to potentially increase, decrease or maintain oxygen between monthly visits.

Parents will transmit a minimum of 4 days of stored RHO data (min 8 hrs per day) every 4-7 days. Changes in oxygen needs will be made based on standardized objective criteria. To determine discontinuation of oxygen, RHO will be utilized instead of polysomnography.

RHO: Recorded oximetry data will be downloaded from home oximeters, analyzed, and used to assist in supplemental oxygen weaning decisions.

Period Title: Overall Study
Started 99 97
Completed 74 67
Not Completed 25 30
Reason Not Completed
Death             1             0
Withdrawal by Subject             9             14
Physician Decision             2             2
Lost to Follow-up             8             10
6 Month Follow-up Not Complete             5             4
Arm/Group Title Arm A:Standard Therapy Arm B:RHO Total
Hide Arm/Group Description Infants' oxygen will be increased, decreased, or maintained based on brief structured assessments during monthly clinic visits. Polysomnograms will be utilized prior to final discontinuation of oxygen. RHO will only be utilized on the night prior to and during the polysomnogram to compare these two modalities.

Infants will have the same monthly clinic assessments as in Arm A, but also will utilize RHO to potentially increase, decrease or maintain oxygen between monthly visits.

Parents will transmit a minimum of 4 days of stored RHO data (min 8 hrs per day) every 4-7 days. Changes in oxygen needs will be made based on standardized objective criteria. To determine discontinuation of oxygen, RHO will be utilized instead of polysomnography.

RHO: Recorded oximetry data will be downloaded from home oximeters, analyzed, and used to assist in supplemental oxygen weaning decisions.

Total of all reporting groups
Overall Number of Baseline Participants 99 97 196
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Less than 1 Year of Age Number Analyzed 99 participants 97 participants 196 participants
99
 100.0%
97
 100.0%
196
 100.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants 97 participants 196 participants
Female
41
  41.4%
33
  34.0%
74
  37.8%
Male
58
  58.6%
64
  66.0%
122
  62.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants 97 participants 196 participants
Hispanic or Latino
12
  12.1%
6
   6.2%
18
   9.2%
Not Hispanic or Latino
61
  61.6%
65
  67.0%
126
  64.3%
Unknown or Not Reported
26
  26.3%
26
  26.8%
52
  26.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants 97 participants 196 participants
American Indian or Alaska Native
0
   0.0%
1
   1.0%
1
   0.5%
Asian
1
   1.0%
4
   4.1%
5
   2.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
12
  12.1%
13
  13.4%
25
  12.8%
White
57
  57.6%
59
  60.8%
116
  59.2%
More than one race
7
   7.1%
5
   5.2%
12
   6.1%
Unknown or Not Reported
22
  22.2%
15
  15.5%
37
  18.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 99 participants 97 participants 196 participants
99 97 196
Respiratory Support at 36 Weeks  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants 97 participants 196 participants
Mechanical Ventilation
3
   3.0%
6
   6.2%
9
   4.6%
Non-Invasive Positive Pressure (CPAP/HFNC)
52
  52.5%
48
  49.5%
100
  51.0%
Low-Flow Nasal Cannula (LFNC)
36
  36.4%
32
  33.0%
68
  34.7%
Room Air
2
   2.0%
5
   5.2%
7
   3.6%
Unknown
6
   6.1%
6
   6.2%
12
   6.1%
Diuretics  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants 97 participants 196 participants
Yes
52
  52.5%
51
  52.6%
103
  52.6%
No
41
  41.4%
38
  39.2%
79
  40.3%
Unknowns
6
   6.1%
8
   8.2%
14
   7.1%
Birth Weight  
Mean (Standard Deviation)
Unit of measure:  Grams
Number Analyzed 99 participants 97 participants 196 participants
938.2  (439.1) 929.5  (442.6) 933.9  (439.6)
Gestational Age (wks)  
Mean (Standard Deviation)
Unit of measure:  Birth Gestational Age (Weeks)
Number Analyzed 99 participants 97 participants 196 participants
26.9  (2.6) 26.9  (2.7) 26.9  (2.6)
Length of NICU Stay (days)  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 99 participants 97 participants 196 participants
97.7  (33.4) 104.4  (36.7) 101  (35.1)
1.Primary Outcome
Title Duration of Home Oxygen Therapy
Hide Description Duration of home oxygen use from time of randomization (baseline visit) to successful discontinuation of home oxygen therapy (HOT).
Time Frame NICU discharge date until successful discontinuation of home oxygen therapy (HOT), up to 26 months.
Hide Outcome Measure Data
Hide Analysis Population Description
A total of 166 infants were weaned successfully from HOT using one of our two methods, and a total of 140 subjects completed all study procedures through six months of follow-up post discontinuation of HOT. A total of 30 subjects were not weaned using either method due to being lost to follow-up, withdrawing, or parents self-weaning subject.
Arm/Group Title Arm A:Standard Therapy Arm B:RHO
Hide Arm/Group Description:
Infants' oxygen will be increased, decreased, or maintained based on brief structured assessments during monthly clinic visits. Polysomnograms will be utilized prior to final discontinuation of oxygen. RHO will only be utilized on the night prior to and during the polysomnogram to compare these two modalities.

Infants will have the same monthly clinic assessments as in Arm A, but also will utilize RHO to potentially increase, decrease or maintain oxygen between monthly visits.

Parents will transmit a minimum of 4 days of stored RHO data (min 8 hrs per day) every 4-7 days. Changes in oxygen needs will be made based on standardized objective criteria. To determine discontinuation of oxygen, RHO will be utilized instead of polysomnography.

RHO: Recorded oximetry data will be downloaded from home oximeters, analyzed, and used to assist in supplemental oxygen weaning decisions.

Overall Number of Participants Analyzed 87 79
Median (90% Confidence Interval)
Unit of Measure: Days
66
(42 to 113)
58
(24 to 127)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A:Standard Therapy, Arm B:RHO
Comments The trial was designed to have 97% power at a type I error rate of 5% to detect a 25% intervention effect with respect to the primary outcome. this was done using an independent sample t-test. P-value was calculated, and a p-value of 0.05 or less was interpreted as statistically significant result.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.03
Comments A two-sided P-value of 0.05 or less was interpreted as a statistically significant result.
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Caregiver Quality of Life
Hide Description We will compare the difference between survey-derived quality-of-life scores, comparing parent response averages while on home oxygen therapy (HOT) versus 3 months post oxygen discontinuation scores in both arms. The infant scale is composed of 36 items comprising 5 dimensions. The item scaling is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores range from 0 to 100, with a higher score indicating a higher parent satisfaction and quality of life.
Time Frame Monthly while on home oxygen therapy and at 3 months post discontinuation of therapy
Hide Outcome Measure Data
Hide Analysis Population Description
The final cohort included 196 infants, of those infants 105 parents completed at least one pre-parent satisfactory survey and one post-survey.
Arm/Group Title Arm A:Standard Therapy Arm B:RHO
Hide Arm/Group Description:
Infants' oxygen will be increased, decreased, or maintained based on brief structured assessments during monthly clinic visits. Polysomnograms will be utilized prior to final discontinuation of oxygen. RHO will only be utilized on the night prior to and during the polysomnogram to compare these two modalities.

Infants will have the same monthly clinic assessments as in Arm A, but also will utilize RHO to potentially increase, decrease or maintain oxygen between monthly visits.

Parents will transmit a minimum of 4 days of stored RHO data (min 8 hrs per day) every 4-7 days. Changes in oxygen needs will be made based on standardized objective criteria. To determine discontinuation of oxygen, RHO will be utilized instead of polysomnography.

RHO: Recorded oximetry data will be downloaded from home oximeters, analyzed, and used to assist in supplemental oxygen weaning decisions.

Overall Number of Participants Analyzed 51 54
Mean (Standard Deviation)
Unit of Measure: score on a scale
Pre-Wean from HOT 74.5  (16.3) 70.4  (15.0)
Post-Wean from HOT 78.6  (18.6) 75.9  (17.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A:Standard Therapy, Arm B:RHO
Comments Power calculations were based on the primary analysis (t-test comparing changes). A sample size of 130 would have given 80% power, with 0.05 two sided type 1 error rate, to detect a 20% absolute difference in emotional role limitation on the PedsQL v2.0, which we considered to be statistically significant.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.38
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Secondary Outcome
Title Participants With Respiratory-related Emergency Department Visits and Rehospitalizations
Hide Description We will assess rates of rehospitalization or ED visit throughout the weaning process and continue to assess until 6 months post discontinuation.
Time Frame WIthin 6 months of discontinuation of home oxygen
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A:Standard Therapy Arm B:RHO
Hide Arm/Group Description:
Infants' oxygen will be increased, decreased, or maintained based on brief structured assessments during monthly clinic visits. Polysomnograms will be utilized prior to final discontinuation of oxygen. RHO will only be utilized on the night prior to and during the polysomnogram to compare these two modalities.

Infants will have the same monthly clinic assessments as in Arm A, but also will utilize RHO to potentially increase, decrease or maintain oxygen between monthly visits.

Parents will transmit a minimum of 4 days of stored RHO data (min 8 hrs per day) every 4-7 days. Changes in oxygen needs will be made based on standardized objective criteria. To determine discontinuation of oxygen, RHO will be utilized instead of polysomnography.

RHO: Recorded oximetry data will be downloaded from home oximeters, analyzed, and used to assist in supplemental oxygen weaning decisions.

Overall Number of Participants Analyzed 99 97
Measure Type: Number
Unit of Measure: participants
All Events 41 25
Serious Adverse Event 28 19
Life Threatening, ICU admission or Intubation (G4) 7 6
Hospitalization (G3) 30 19
Intervention without hospitalization 39 26
Event During Respiratory Virus Season 29 17
Event During Non-Respiratory Season 26 15
Respiratory Related Events 26 20
Non-Respiratory Related Events 25 14
4.Secondary Outcome
Title Growth Parameters
Hide Description Growth measurements were taken at each monthly clinic visit while on oxygen. The average for weight z-score change was calculated for each subject while on oxygen therapy. After oxygen discontinuation, growth measurements were taken at the 1 month and 6 month post wean visits. These two measurements were again averaged for each patient. The weight z-score change was found in both arms for pre and post weaning from home oxygen therapy. The weight z-score indicates the number of standard deviations away from the mean a participants weight is. A z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
Time Frame Enrollment to 6 months post home oxygen therapy discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
We had data for 87 and 72 infants in the standard of care arm and RHO arm, respectively, during the O2 weaning process, and 80 and 73 infants after O2 discontinuation.
Arm/Group Title Arm A: Standard of Care, Pre-Weaning Arm B: Intervention Arm; Pre-Weaning Arm A: Standard of Care; Post-Weaning Arm B: Intervention Arm; Post-Weaning
Hide Arm/Group Description:
Growth assessments were documented at each monthly clinic visit while on oxygen. Infants who had at least one assessment were included in the analysis.
Growth assessments were documented at each monthly clinic visit while on oxygen. Infants who had at least one assessment were included in the analysis.
Growth assessments were documented at the one and six month follow-up visits. Infants who had at least one assessment were included in the analysis.
Growth assessments were documented at the one and six month follow-up visits. Infants who had at least one assessment were included in the analysis.
Overall Number of Participants Analyzed 87 72 80 73
Mean (Standard Deviation)
Unit of Measure: Weight z-score change
-0.13  (0.03) -0.01  (0.03) 0.02  (0.03) 0.03  (0.03)
5.Secondary Outcome
Title Growth Parameters, Weight-for-length Z-score Change
Hide Description Growth measurements were taken at each monthly clinic visit while on oxygen. The average for weight for length z-score change was calculated for each subject while on oxygen therapy. After oxygen discontinuation, growth measurements were taken at the 1 month and 6 month post wean visits. These two measurements were again averaged for each patient. The weight for length z-score change was found in both arms for pre and post weaning from home oxygen therapy.The weight-for-length z-score indicates the number of standard deviations away from the mean a participants weight is. A z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.
Time Frame Enrollment through 6 months post discontinuation of home oxygen therapy
Hide Outcome Measure Data
Hide Analysis Population Description
We had data for 87 and 72 infants in the standard of care arm and RHO arm, respectively, during the O2 weaning process, and 80 and 73 infants after O2 discontinuation.
Arm/Group Title Arm A: Standard of Care, Pre-Weaning Arm B: Intervention Arm; Pre-Weaning Arm A: Standard of Care; Post-Weaning Arm B: Intervention Arm; Post-Weaning
Hide Arm/Group Description:
Growth assessments were documented at each monthly clinic visit while on oxygen. Infants who had at least one assessment were included in the analysis.
Growth assessments were documented at each monthly clinic visit while on oxygen. Infants who had at least one assessment were included in the analysis.
Growth assessments were documented at the one month and six month post wean follow-up visits. Infants who had at least one assessment in the follow-up period were included in the analysis.
Growth assessments were documented at the one month and six month post wean follow-up visits. Infants who had at least one assessment in the follow-up period were included in the analysis.
Overall Number of Participants Analyzed 87 72 80 73
Mean (Standard Error)
Unit of Measure: Weight-for-Length z-score change
-0.17  (0.06) -0.06  (0.07) -0.14  (0.07) 0.01  (0.07)
Time Frame Adverse events were tracked from enrollment until 6 months post home oxygen therapy discontinuation.
Adverse Event Reporting Description Grade 1: No Intervention Grade 2: Intervention without hospitalization concomitant-drug/non-drug therapy Grade 3: Hospitalization (Serious Adverse Event) Grade 4: Life Threatening, ICU Admission, Intubation (Serious Adverse Event) Grade 5: Death (Serious Adverse Event)
 
Arm/Group Title Arm A:Standard Therapy Arm B:RHO
Hide Arm/Group Description Infants' oxygen will be increased, decreased, or maintained based on brief structured assessments during monthly clinic visits. Polysomnograms will be utilized prior to final discontinuation of oxygen. RHO will only be utilized on the night prior to and during the polysomnogram to compare these two modalities.

Infants will have the same monthly clinic assessments as in Arm A, but also will utilize RHO to potentially increase, decrease or maintain oxygen between monthly visits.

Parents will transmit a minimum of 4 days of stored RHO data (min 8 hrs per day) every 4-7 days. Changes in oxygen needs will be made based on standardized objective criteria. To determine discontinuation of oxygen, RHO will be utilized instead of polysomnography.

RHO: Recorded oximetry data will be downloaded from home oximeters, analyzed, and used to assist in supplemental oxygen weaning decisions.

All-Cause Mortality
Arm A:Standard Therapy Arm B:RHO
Affected / at Risk (%) Affected / at Risk (%)
Total   41/99 (41.41%)      26/97 (26.80%)    
Hide Serious Adverse Events
Arm A:Standard Therapy Arm B:RHO
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   28/99 (28.28%)      19/97 (19.59%)    
Gastrointestinal disorders     
Feeding Issue/G-Tube Complication   8/99 (8.08%)  8 1/97 (1.03%)  2
Respiratory, thoracic and mediastinal disorders     
Viral Respiratory Event  [1]  16/99 (16.16%)  22 18/97 (18.56%)  20
Other  [2]  4/99 (4.04%)  10 0/97 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Former preterm infants are at an increased risk for respiratory adverse events and morbidity.
[2]
Other serious adverse events related to prematurity
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm A:Standard Therapy Arm B:RHO
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/99 (13.13%)      10/97 (10.31%)    
Respiratory, thoracic and mediastinal disorders     
Respiratory Related Event   13/99 (13.13%)  15 10/97 (10.31%)  11
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Lawrence Rhein
Organization: University of Massachusetts Medical School
Phone: 508-334-6206
EMail: Lawrence.Rhein@umassmemorial.org
Layout table for additonal information
Responsible Party: Lawrence Rhein, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT01994954    
Other Study ID Numbers: IP00009772
First Submitted: November 20, 2013
First Posted: November 26, 2013
Results First Submitted: February 1, 2019
Results First Posted: October 2, 2019
Last Update Posted: October 2, 2019