Premature Infants
Conditions
Keywords
newborn intensive care unit, NICU, supplemental oxygen
Brief summary
The investigators hypothesize that Recorded Home Oximetry (RHO) utilization will not increase rates of respiratory-related re-hospitalizations and ED visits, and will not impair growth compared to standard oxygen management protocols. Evidence-based specific consensus guidelines for home regulated oxygen management do not currently exist. Current strategies for infants requiring outpatient supplemental home oxygen include brief checks of oxygen status during monthly clinic visits. Although the infants stay on monitors, no data in between visits is obtained to ensure that infants can maintain oxygen levels after weans are made. Before finally allowing oxygen to be removed, many centers also require an overnight sleep study in the hospital, to make sure that the infant's oxygen levels stay safe when the infant is in deep sleep. Because these methods rely solely on assumptions rather than individually recorded data, an infant's time on supplemental oxygen may be prolonged or insufficient. This study will evaluate both the currently used accepted therapy and a method of weaning that involves recording and sending oxygen data for analysis in between clinic visits. Premature infants who require home oxygen therapy at time of discharge who meet eligibility criteria will be randomized into two arms: Arm A (Standard therapy): Infants' oxygen will be increased, decreased, or maintained based on brief structured assessments during monthly clinic visits. Arm B (Recorded Home Oximetry (RHO)): Infants will have the same monthly clinic assessments as in Arm A, but also will utilize Recorded Home Oximetry (RHO) to potentially increase, decrease or maintain oxygen between monthly visits. Parents of all infants will be interviewed using structured quality-of-life questionnaires at the beginning and ending of the oxygen management process. Health care utilization (emergency department visits and rehospitalizations) and growth will be assessed 6 months after discontinuation of oxygen. The investigators overall objective is to determine whether Recorded Home Oximetry (RHO) can improve caregiver quality of life, and can shorten Home Oxygen Therapy (HOT) duration and eliminate need for polysomnogram, without compromising safety. The investigators will determine respiratory-related re-hospitalizations, emergency department (ED) visits, and growth parameters to confirm safety of the proposed weaning strategies.
Interventions
OTHERRHO
Recorded oximetry data will be downloaded from home oximeters, analyzed, and used to assist in supplemental oxygen weaning decisions.
Sponsors
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
University of Massachusetts, Worcester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 37 Weeks
Healthy volunteers
No
Inclusion criteria
* Infant with birth gestational age ≤ 37 (37 0/7) wks postmenstrual age (PMA) who has requirement for supplemental O2 at time of NICU discharge, as determined by primary NICU team. * Infant receiving pediatric pulmonology care at the Center for Healthy Infant Lung Development * Parent aged 18 years or older * English or Spanish-speaking.
Exclusion criteria
* Parents whose infants has presence of pulmonary hypertension at enrollment * Parents whose infant with syndrome or other diagnosis with known high risk for persistent hypoxia (cardiac disease, Trisomy 21, Pierre-Robin Sequence, etc.) * Parents whose infant has requirement for O2 flow rate \> 1 L/min or tracheostomy * Any infants who also require caffeine at discharge from the NICU
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Home Oxygen Therapy | NICU discharge date until successful discontinuation of home oxygen therapy (HOT), up to 26 months. | Duration of home oxygen use from time of randomization (baseline visit) to successful discontinuation of home oxygen therapy (HOT). |
| Caregiver Quality of Life | Monthly while on home oxygen therapy and at 3 months post discontinuation of therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | 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. |
| Growth Parameters | Enrollment to 6 months post home oxygen therapy 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. |
| Growth Parameters, Weight-for-length Z-score Change | Enrollment through 6 months post discontinuation of home oxygen therapy | 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. |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 99 |
| 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. | 97 |
| Total | 196 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | 6 Month Follow-up Not Complete | 5 | 4 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 8 | 10 |
| Overall Study | Physician Decision | 2 | 2 |
| Overall Study | Withdrawal by Subject | 9 | 14 |
Baseline characteristics
| Characteristic | Arm A:Standard Therapy | Arm B:RHO | Total |
|---|---|---|---|
| Age, Customized Less than 1 Year of Age | 99 Participants | 97 Participants | 196 Participants |
| Birth Weight | 938.2 grams STANDARD_DEVIATION 439.1 | 929.5 grams STANDARD_DEVIATION 442.6 | 933.9 grams STANDARD_DEVIATION 439.6 |
| Diuretics No | 41 Participants | 38 Participants | 79 Participants |
| Diuretics Unknowns | 6 Participants | 8 Participants | 14 Participants |
| Diuretics Yes | 52 Participants | 51 Participants | 103 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 6 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 65 Participants | 126 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 26 Participants | 26 Participants | 52 Participants |
| Gestational Age (wks) | 26.9 Birth Gestational Age (Weeks) STANDARD_DEVIATION 2.6 | 26.9 Birth Gestational Age (Weeks) STANDARD_DEVIATION 2.7 | 26.9 Birth Gestational Age (Weeks) STANDARD_DEVIATION 2.6 |
| Length of NICU Stay (days) | 97.7 days STANDARD_DEVIATION 33.4 | 104.4 days STANDARD_DEVIATION 36.7 | 101 days STANDARD_DEVIATION 35.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 13 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 5 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 22 Participants | 15 Participants | 37 Participants |
| Race (NIH/OMB) White | 57 Participants | 59 Participants | 116 Participants |
| Region of Enrollment United States | 99 participants | 97 participants | 196 participants |
| Respiratory Support at 36 Weeks Low-Flow Nasal Cannula (LFNC) | 36 Participants | 32 Participants | 68 Participants |
| Respiratory Support at 36 Weeks Mechanical Ventilation | 3 Participants | 6 Participants | 9 Participants |
| Respiratory Support at 36 Weeks Non-Invasive Positive Pressure (CPAP/HFNC) | 52 Participants | 48 Participants | 100 Participants |
| Respiratory Support at 36 Weeks Room Air | 2 Participants | 5 Participants | 7 Participants |
| Respiratory Support at 36 Weeks Unknown | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 41 Participants | 33 Participants | 74 Participants |
| Sex: Female, Male Male | 58 Participants | 64 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 41 / 99 | 26 / 97 |
| other Total, other adverse events | 13 / 99 | 10 / 97 |
| serious Total, serious adverse events | 28 / 99 | 19 / 97 |
Outcome results
Primary
Caregiver Quality of Life
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
Population: The final cohort included 196 infants, of those infants 105 parents completed at least one pre-parent satisfactory survey and one post-survey.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A:Standard Therapy | Caregiver Quality of Life | Pre-Wean from HOT | 74.5 score on a scale | Standard Deviation 16.3 |
| Arm A:Standard Therapy | Caregiver Quality of Life | Post-Wean from HOT | 78.6 score on a scale | Standard Deviation 18.6 |
| Arm B:RHO | Caregiver Quality of Life | Pre-Wean from HOT | 70.4 score on a scale | Standard Deviation 15 |
| Arm B:RHO | Caregiver Quality of Life | Post-Wean from HOT | 75.9 score on a scale | Standard Deviation 17.4 |
Comparison: 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.p-value: 0.38Wilcoxon (Mann-Whitney)
Primary
Duration of Home Oxygen Therapy
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.
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A:Standard Therapy | Duration of Home Oxygen Therapy | 66 Days |
| Arm B:RHO | Duration of Home Oxygen Therapy | 58 Days |
Comparison: 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.p-value: <0.03t-test, 2 sided
Secondary
Growth Parameters
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A:Standard Therapy | Growth Parameters | -0.13 Weight z-score change | Standard Deviation 0.03 |
| Arm B:RHO | Growth Parameters | -0.01 Weight z-score change | Standard Deviation 0.03 |
| Arm A: Standard of Care; Post-Weaning | Growth Parameters | 0.02 Weight z-score change | Standard Deviation 0.03 |
| Arm B: Intervention Arm; Post-Weaning | Growth Parameters | 0.03 Weight z-score change | Standard Deviation 0.03 |
Secondary
Growth Parameters, Weight-for-length Z-score Change
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A:Standard Therapy | Growth Parameters, Weight-for-length Z-score Change | -0.17 Weight-for-Length z-score change | Standard Error 0.06 |
| Arm B:RHO | Growth Parameters, Weight-for-length Z-score Change | -0.06 Weight-for-Length z-score change | Standard Error 0.07 |
| Arm A: Standard of Care; Post-Weaning | Growth Parameters, Weight-for-length Z-score Change | -0.14 Weight-for-Length z-score change | Standard Error 0.07 |
| Arm B: Intervention Arm; Post-Weaning | Growth Parameters, Weight-for-length Z-score Change | 0.01 Weight-for-Length z-score change | Standard Error 0.07 |
Secondary
Participants With Respiratory-related Emergency Department Visits and Rehospitalizations
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A:Standard Therapy | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Serious Adverse Event | 28 participants |
| Arm A:Standard Therapy | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Event During Respiratory Virus Season | 29 participants |
| Arm A:Standard Therapy | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Hospitalization (G3) | 30 participants |
| Arm A:Standard Therapy | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Event During Non-Respiratory Season | 26 participants |
| Arm A:Standard Therapy | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Life Threatening, ICU admission or Intubation (G4) | 7 participants |
| Arm A:Standard Therapy | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Respiratory Related Events | 26 participants |
| Arm A:Standard Therapy | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Intervention without hospitalization | 39 participants |
| Arm A:Standard Therapy | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Non-Respiratory Related Events | 25 participants |
| Arm A:Standard Therapy | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | All Events | 41 participants |
| Arm B:RHO | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Non-Respiratory Related Events | 14 participants |
| Arm B:RHO | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | All Events | 25 participants |
| Arm B:RHO | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Serious Adverse Event | 19 participants |
| Arm B:RHO | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Life Threatening, ICU admission or Intubation (G4) | 6 participants |
| Arm B:RHO | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Hospitalization (G3) | 19 participants |
| Arm B:RHO | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Intervention without hospitalization | 26 participants |
| Arm B:RHO | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Event During Respiratory Virus Season | 17 participants |
| Arm B:RHO | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Event During Non-Respiratory Season | 15 participants |
| Arm B:RHO | Participants With Respiratory-related Emergency Department Visits and Rehospitalizations | Respiratory Related Events | 20 participants |