Target Oxygen Ranges in Infants With Pulmonary Hypertension (TORPH)

• ClinicalTrials.gov Identifier: NCT06373289
• Recruitment Status: Not yet recruiting
• First Posted: April 18, 2024
• Last Update Posted: April 18, 2024
• Sponsor: University of Alabama at Birmingham
• Information provided by (Responsible Party): Samuel Gentle, University of Alabama at Birmingham

Tracking Information

• First Submitted Date: March 19, 2024
• First Posted Date: April 18, 2024
• Last Update Posted Date: April 18, 2024
• Estimated Study Start Date: July 1, 2025
• Estimated Primary Completion Date: July 1, 2029 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 17, 2024)

Intermittent hypoxemia event duration [ Time Frame: From date of randomization until 5 weeks have elapsed or date of discharge, whichever came first ]

The average duration of time (in seconds) an infant's oxygen saturation decrease below 80%.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 17, 2024)

• Echocardiographic shunting [ Time Frame: through study completion, 5 weeksFrom date of randomization until 5 weeks have elapsed or date of discharge, whichever came first ]
  >20% flow of blood across the PDA from the pulmonary to arterial circulation
• Echocardiographic interventricular septal flattening [ Time Frame: From date of randomization until 5 weeks have elapsed or date of discharge, whichever came first ]
  End-systolic flattening of the interventricular septum (eccentricity index >1.3)
• Echocardiographic tricuspid regurgitation [ Time Frame: From date of randomization until 5 weeks have elapsed or date of discharge, whichever came first ]
  Right ventricular pressure estimates
• Intermittent hypoxemia frequency [ Time Frame: From date of randomization until 5 weeks have elapsed or date of discharge, whichever came first ]
  Number of daily events during which an infant's oxygen saturation decreases below 80%
• Cumulative hypoxemia [ Time Frame: From date of randomization until 5 weeks have elapsed or date of discharge, whichever came first ]
  Daily duration during which an infant's oxygen saturation is <80%
• Brain natriuretic peptide [ Time Frame: From date of randomization until 5 weeks have elapsed or date of discharge, whichever came first ]
  A polypeptide released from the cardiac ventricles indicative of right heart strain

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Target Oxygen Ranges in Infants With Pulmonary Hypertension
• Official Title: Target Oxygen Saturation Ranges in Infants With Bronchopulmonary Dysplasia Associated Pulmonary Hypertension
• Brief Summary: Around 50% of infants born extremely preterm develop a chronic lung disease known as bronchopulmonary dysplasia of which some infants will also develop pulmonary hypertension of which 50% of children will die before the age of 2. Physicians are currently limited in their ability to select the most appropriate oxygen targets that will improve outcomes in infants with this condition. This clinical trial will determine whether using different amounts of oxygen improve outcomes in infants with this disease.

Detailed Description

Infants born between 22.0 to 31.6 weeks' gestational age with bronchopulmonary dysplasia associated pulmonary hypertension, are receiving supplemental oxygen, and have prethreshold retinopathy of prematurity in at least one eye or have mature retinas will be randomized to SpO2 targets of either (1) 92-95% (control) or (2) 95-98% (intervention).

Using a cross over design with a 1:1 parallel allocation of infants randomized using a stratified permuted block design. Following 2 weeks of exposure A, infants will cross over to exposure B for 2 weeks with a 1-week washout period. Bedside providers will follow pre-specified algorithms to maintain oxygen targets during the randomization period. Reports of oxygen saturation performance will also be provided to bedside providers through oxygen saturation histograms.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

Single center, randomized cross-over pilot study with a 1:1 parallel allocation of infants to SpO2 targets of 92-95% (control) and 95-98% (intervention) using a stratified permuted block design. Following 2 weeks of exposure A, infants will cross over to exposure B for 2 weeks with a 1-week washout period.

Masking: Single (Outcomes Assessor)
Masking Description:

The PI will perform bedside echocardiography precluding masking to group allocation. All echocardiograms will be further reviewed by a cardiologist masked to group allocation with additional cardiologist review in instances of disagreement. Inter-rater reliability testing will also be performed.

Primary Purpose: Treatment

Condition

• Bronchopulmonary Dysplasia
• Pulmonary Hypertension

Intervention

• Device: higher oxygen saturation target using Nellcor pulse oximetry sensors
  The intervention will be a cross over exposure to the higher oxygen saturation target.
• Device: lower oxygen saturation target using Nellcor pulse oximetry sensors
  The intervention will be a cross over exposure to the lower oxygen saturation target.

Study Arms

• Active Comparator: Oxygen saturation target 92-95%
  At UAB oxygen saturation targeting is achieved using systematic oxygen saturation histogram monitoring every 3-4 hours by nurse, respiratory therapists, and physicians. Upon randomization to this arm, infants oxygen saturation alarm limits will be adjusted to 92-95% after which an FiO2 modification algorithm will be employed to maintain targets. Daily compliance reports will be generated to ensure oxygen saturation achievement corresponds with oxygen saturation targets. Infants will be exposed for a 2 week period after which they will crossover to the alternative oxygen saturation target with a 1 week washout period in between targets.
  Intervention: Device: lower oxygen saturation target using Nellcor pulse oximetry sensors
• Active Comparator: Oxygen saturation target 95-98%
  At UAB oxygen saturation targeting is achieved using systematic oxygen saturation histogram monitoring every 3-4 hours by nurse, respiratory therapists, and physicians. Upon randomization to this arm, infants oxygen saturation alarm limits will be adjusted to 95-98% after which an FiO2 modification algorithm will be employed to maintain targets. Daily compliance reports will be generated to ensure oxygen saturation achievement corresponds with oxygen saturation targets. Infants will be exposed for a 2 week period after which they will crossover to the alternative oxygen saturation target with a 1 week washout period in between targets.
  Intervention: Device: higher oxygen saturation target using Nellcor pulse oximetry sensors

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: April 17, 2024): 39
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 1, 2030
• Estimated Primary Completion Date: July 1, 2029 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Between 22w 0/7d and 31w 6/7d gestation at birth
• Diagnosed with echocardiographic pulmonary hypertension (1) >20% flow of blood across the PDA from the pulmonary to arterial circulation, (2) end-systolic flattening of the interventricular septum (eccentricity index >1.3), or (3) right ventricular pressure estimates ≥ 35 mm Hg
• Receiving supplemental oxygen
• Have prethreshold retinopathy of prematurity in at least one eye or have mature retinas

Exclusion Criteria:

• Major congenital anomalies

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Months to 5 Months (Child)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Samuel Gentle, MD; 205-541-2247; samjgentle@gmail.com

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT06373289
• Other Study ID Numbers: 000539476; 1K23HD113837-01A1 ( Other Identifier: NICHD (pending) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Samuel Gentle, University of Alabama at Birmingham
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Alabama at Birmingham
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Samuel Gentle; University of Alabama at Birmingham

• PRS Account: University of Alabama at Birmingham
• Verification Date: April 2024