Trial Outcomes & Findings for A Randomized Trial of Outpatient Oxygen Weaning Strategies in Premature Infants (NCT NCT01994954)

NCT ID: NCT01994954

Last Updated: 2023-05-30

Results Overview

Duration of home oxygen use from time of randomization (baseline visit) to successful discontinuation of home oxygen therapy (HOT).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 196 participants
• Primary outcome timeframe: NICU discharge date until successful discontinuation of home oxygen therapy (HOT), up to 26 months.
• Results posted on: 2023-05-30

Participant Flow

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.

Participant milestones

Measure	Arm A:Standard Therapy 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.	Arm B:RHO 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 Study STARTED	99	97
Overall Study COMPLETED	74	67
Overall Study NOT COMPLETED	25	30

Reasons for withdrawal

Measure	Arm A:Standard Therapy 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.	Arm B:RHO 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 Study Death	1	0
Overall Study Withdrawal by Subject	9	14
Overall Study Physician Decision	2	2
Overall Study Lost to Follow-up	8	10
Overall Study 6 Month Follow-up Not Complete	5	4

Baseline Characteristics

A Randomized Trial of Outpatient Oxygen Weaning Strategies in Premature Infants

Baseline characteristics by cohort

Measure	Arm A:Standard Therapy n=99 Participants 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.	Arm B:RHO n=97 Participants 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 n=196 Participants Total of all reporting groups
Age, Customized Less than 1 Year of Age	99 Participants n=5 Participants	97 Participants n=7 Participants	196 Participants n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	33 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	64 Participants n=7 Participants	122 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	6 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	61 Participants n=5 Participants	65 Participants n=7 Participants	126 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) White	57 Participants n=5 Participants	59 Participants n=7 Participants	116 Participants n=5 Participants
Race (NIH/OMB) More than one race	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	22 Participants n=5 Participants	15 Participants n=7 Participants	37 Participants n=5 Participants
Region of Enrollment United States	99 participants n=5 Participants	97 participants n=7 Participants	196 participants n=5 Participants
Respiratory Support at 36 Weeks Mechanical Ventilation	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Respiratory Support at 36 Weeks Non-Invasive Positive Pressure (CPAP/HFNC)	52 Participants n=5 Participants	48 Participants n=7 Participants	100 Participants n=5 Participants
Respiratory Support at 36 Weeks Low-Flow Nasal Cannula (LFNC)	36 Participants n=5 Participants	32 Participants n=7 Participants	68 Participants n=5 Participants
Respiratory Support at 36 Weeks Room Air	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Respiratory Support at 36 Weeks Unknown	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Diuretics Yes	52 Participants n=5 Participants	51 Participants n=7 Participants	103 Participants n=5 Participants
Diuretics No	41 Participants n=5 Participants	38 Participants n=7 Participants	79 Participants n=5 Participants
Diuretics Unknowns	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Birth Weight	938.2 grams STANDARD_DEVIATION 439.1 • n=5 Participants	929.5 grams STANDARD_DEVIATION 442.6 • n=7 Participants	933.9 grams STANDARD_DEVIATION 439.6 • n=5 Participants
Gestational Age (wks)	26.9 Birth Gestational Age (Weeks) STANDARD_DEVIATION 2.6 • n=5 Participants	26.9 Birth Gestational Age (Weeks) STANDARD_DEVIATION 2.7 • n=7 Participants	26.9 Birth Gestational Age (Weeks) STANDARD_DEVIATION 2.6 • n=5 Participants
Length of NICU Stay (days)	97.7 days STANDARD_DEVIATION 33.4 • n=5 Participants	104.4 days STANDARD_DEVIATION 36.7 • n=7 Participants	101 days STANDARD_DEVIATION 35.1 • n=5 Participants

PRIMARY outcome

Timeframe: NICU discharge date until successful discontinuation of home oxygen therapy (HOT), up to 26 months.

Population: 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.

Duration of home oxygen use from time of randomization (baseline visit) to successful discontinuation of home oxygen therapy (HOT).

Outcome measures

Measure	Arm A:Standard Therapy n=87 Participants 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.	Arm B:RHO n=79 Participants 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.	Arm A: Standard of Care; Post-Weaning 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.	Arm B: Intervention Arm; Post-Weaning 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.
Duration of Home Oxygen Therapy	66 Days Interval 42.0 to 113.0	58 Days Interval 24.0 to 127.0	—	—

PRIMARY outcome

Timeframe: Monthly while on home oxygen therapy and at 3 months post discontinuation of therapy

Population: The final cohort included 196 infants, of those infants 105 parents completed at least one pre-parent satisfactory survey and one post-survey.

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.

Outcome measures

Measure	Arm A:Standard Therapy n=51 Participants 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.	Arm B:RHO n=54 Participants 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.	Arm A: Standard of Care; Post-Weaning 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.	Arm B: Intervention Arm; Post-Weaning 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.
Caregiver Quality of Life Pre-Wean from HOT	74.5 score on a scale Standard Deviation 16.3	70.4 score on a scale Standard Deviation 15.0	—	—
Caregiver Quality of Life Post-Wean from HOT	78.6 score on a scale Standard Deviation 18.6	75.9 score on a scale Standard Deviation 17.4	—	—

SECONDARY outcome

Timeframe: WIthin 6 months of discontinuation of home oxygen

We will assess rates of rehospitalization or ED visit throughout the weaning process and continue to assess until 6 months post discontinuation.

Outcome measures

Measure	Arm A:Standard Therapy n=99 Participants 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.	Arm B:RHO n=97 Participants 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.	Arm A: Standard of Care; Post-Weaning 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.	Arm B: Intervention Arm; Post-Weaning 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.
Participants With Respiratory-related Emergency Department Visits and Rehospitalizations Life Threatening, ICU admission or Intubation (G4)	7 participants	6 participants	—	—
Participants With Respiratory-related Emergency Department Visits and Rehospitalizations All Events	41 participants	25 participants	—	—
Participants With Respiratory-related Emergency Department Visits and Rehospitalizations Serious Adverse Event	28 participants	19 participants	—	—
Participants With Respiratory-related Emergency Department Visits and Rehospitalizations Hospitalization (G3)	30 participants	19 participants	—	—
Participants With Respiratory-related Emergency Department Visits and Rehospitalizations Intervention without hospitalization	39 participants	26 participants	—	—
Participants With Respiratory-related Emergency Department Visits and Rehospitalizations Event During Respiratory Virus Season	29 participants	17 participants	—	—
Participants With Respiratory-related Emergency Department Visits and Rehospitalizations Event During Non-Respiratory Season	26 participants	15 participants	—	—
Participants With Respiratory-related Emergency Department Visits and Rehospitalizations Respiratory Related Events	26 participants	20 participants	—	—
Participants With Respiratory-related Emergency Department Visits and Rehospitalizations Non-Respiratory Related Events	25 participants	14 participants	—	—

SECONDARY outcome

Timeframe: Enrollment to 6 months post home oxygen therapy discontinuation

Population: 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.

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.

Outcome measures

Measure	Arm A:Standard Therapy n=87 Participants 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.	Arm B:RHO n=72 Participants 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.	Arm A: Standard of Care; Post-Weaning n=80 Participants 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.	Arm B: Intervention Arm; Post-Weaning n=73 Participants 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 Parameters	-0.13 Weight z-score change Standard Deviation 0.03	-0.01 Weight z-score change Standard Deviation 0.03	0.02 Weight z-score change Standard Deviation 0.03	0.03 Weight z-score change Standard Deviation 0.03

SECONDARY outcome

Timeframe: Enrollment through 6 months post discontinuation of home oxygen therapy

Population: 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.

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.

Outcome measures

Measure	Arm A:Standard Therapy n=87 Participants 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.	Arm B:RHO n=72 Participants 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.	Arm A: Standard of Care; Post-Weaning n=80 Participants 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.	Arm B: Intervention Arm; Post-Weaning n=73 Participants 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 Parameters, Weight-for-length Z-score Change	-0.17 Weight-for-Length z-score change Standard Error 0.06	-0.06 Weight-for-Length z-score change Standard Error 0.07	-0.14 Weight-for-Length z-score change Standard Error 0.07	0.01 Weight-for-Length z-score change Standard Error 0.07

Adverse Events

Arm A:Standard Therapy

Serious events: 28 serious events

Other events: 13 other events

Deaths: 41 deaths

Arm B:RHO

Serious events: 19 serious events

Other events: 10 other events

Deaths: 26 deaths

Serious adverse events

Measure	Arm A:Standard Therapy n=99 participants at risk 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.	Arm B:RHO n=97 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Viral Respiratory Event	16.2% 16/99 • Number of events 22 • Adverse events were tracked from enrollment until 6 months post home oxygen therapy discontinuation. 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)	18.6% 18/97 • Number of events 20 • Adverse events were tracked from enrollment until 6 months post home oxygen therapy discontinuation. 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)
Gastrointestinal disorders Feeding Issue/G-Tube Complication	8.1% 8/99 • Number of events 8 • Adverse events were tracked from enrollment until 6 months post home oxygen therapy discontinuation. 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)	1.0% 1/97 • Number of events 2 • Adverse events were tracked from enrollment until 6 months post home oxygen therapy discontinuation. 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)
Respiratory, thoracic and mediastinal disorders Other	4.0% 4/99 • Number of events 10 • Adverse events were tracked from enrollment until 6 months post home oxygen therapy discontinuation. 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)	0.00% 0/97 • Adverse events were tracked from enrollment until 6 months post home oxygen therapy discontinuation. 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)

Other adverse events

Measure	Arm A:Standard Therapy n=99 participants at risk 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.	Arm B:RHO n=97 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Respiratory Related Event	13.1% 13/99 • Number of events 15 • Adverse events were tracked from enrollment until 6 months post home oxygen therapy discontinuation. 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)	10.3% 10/97 • Number of events 11 • Adverse events were tracked from enrollment until 6 months post home oxygen therapy discontinuation. 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)

Additional Information

Dr. Lawrence Rhein

University of Massachusetts Medical School

Phone: 508-334-6206

Email: Lawrence.Rhein@umassmemorial.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place