Prematurity and Respiratory Outcomes Program (PROP)

NCT ID: NCT01435187

Last Updated: 2016-11-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

835 participants

Study Classification

OBSERVATIONAL

Study Start Date

2011-08-31

Study Completion Date

2016-03-31

Brief Summary

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In survivors of extreme prematurity to 36 weeks Post Menstrual Age (PMA), specific biologic, physiologic and clinical data obtained during the initial hospitalization will predict respiratory morbidity as defined by respiratory health care utilization and respiratory symptoms, between discharge and 1 year corrected age.

This protocol describes a collaboratively developed multicenter study of very preterm infants from birth through the time of discharge from the Neonatal Intensive Care Unit (NICU) and up to 1 year of age, corrected for the degree of prematurity.

Detailed Description

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The primary goal of the PROP studies is to identify biomarkers (biochemical, physiological and genetic) and clinical variables that are associated with and thus potentially predictive of pulmonary status in preterm infants up to 1 year corrected age. An objective and validated measure of pulmonary outcome at 1 year does not currently exist. Some promising measures are in development but not yet ready for use in a multi-center large clinical study.

Moreover, the burden of chronic respiratory illness on the infants and their families is of utmost importance. A composite primary outcome of morbidity that is based on serial parental reports of respiratory symptoms, medications, hospitalizations and dependence on technology during the first year of life has been developed.

Data collection for the outcome assessment will be based on interviews conducted with the infant's main caregiver at 3, 6, 9 and 12 months corrected age. The time frame for data collection is based on questions "since last contact." Numerous epidemiological studies of asthma have used parental or self report of symptoms, physician-diagnosed asthma and allergies, or the use of medications (which may abrogate symptoms) as critical outcomes.

Survey items selected for the determination of the primary outcome will be focused on the following four domains, with any positive response to any element identifying morbidity:

1. Respiratory medications: inhaled bronchodilators, inhaled steroids, systemic steroids, methylxanthines, diuretics, pulmonary vasodilators
2. Hospitalizations for cardiopulmonary causes: any hospitalization regardless of duration
3. Symptoms: any wheeze, cough without cold
4. Home technology dependence: use of home oxygen, ventilator or continuous positive airway pressure (CPAP or BiPAP) of any duration since last contact

The primary outcome will be dichotomous, and defined as "No substantial post-prematurity respiratory disease" or "Post-prematurity respiratory disease." To be classified as having post-prematurity respiratory disease, infants must have a positive response in at least 1 of 4 morbidity domains during at least 2 separate parental interviews. Quarterly data collection up to 1 year corrected age will allow us to identify phenotypes based on the trajectory of post-prematurity respiratory disease and how these different trajectories predict later lung function and the diagnosis of asthma, if we continue to follow this cohort of children.

During hospitalization, all centers will obtain samples of tracheal aspirate, urine and saliva (for DNA extraction) from enrolled infants. At 36 weeks PMA, infants will have respiratory assessments dependent upon their respiratory status: i) respiratory inductive plethysmography (RIP) assesses alterations in tidal breathing resulting from reduced lung compliance and airway obstruction, ii) and a room air challenge (RAC).

Conditions

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Prematurity Respiratory Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Infant Pulmonary Function Testing (iPFT)

A standardized method of performing infant PFTs using the raised volume rapid thoracoabdominal compression (RVRTC) technique will be used. This test will be performed on infants at one year (corrected age). The target sample size of 180 studies will represent the largest number of RVRTC PFTs in the preterm population and will enhance study of the relationship between lung function at 1 year of age and clinical and biologic factors associated with respiratory disease. Although the primary PFT measures will be derived from RVRTC, V'maxFRC, respiratory system compliance (Crs) and resistance (Rrs) will also be measured because these can be easily obtained. Crs and Rrs will be obtained using the single breath occlusion method.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Infants who are less than or equal to 7 days old
* Gestational Age (GA) between 23 weeks and 0/7 days and 28 weeks and 6/7 days

Exclusion Criteria

* Infants who meet any of the following conditions will be excluded from the PROP cohort:

1. The infant is not considered to be viable (decision made not to provide life-saving therapies)
2. Congenital heart disease (not including PDA and hemodynamically insignificant VSD or ASD)
3. Structural abnormalities of the upper airway, lungs or chest wall
4. Other congenital malformations or syndromes that adversely affect life expectancy or cardio-pulmonary development
5. Family is unlikely to be available for long-term follow-up
Minimum Eligible Age

1 Day

Maximum Eligible Age

7 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Barbara K Schmidt, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Jonas H Ellenberg, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Gloria S Pryhuber, MD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Alan H Jobe, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cincinnati Childrens Hospital

Aaron Hamvas, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine / St. Louis Children's Hospital

Judy Aschner, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University School of Medicine

Roberta L Keller, MD

Role: PRINCIPAL_INVESTIGATOR

University of California San Francisco/Benioff Children's Hospital

Judith Voynow, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Stephanie D Davis, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University/Riley Hospital for Children

Locations

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Alta Bates Summit Medical Center

Oakland, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Indiana University Health/Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Washington Universitiy

St Louis, Missouri, United States

Site Status

University of Buffalo

Buffalo, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cincinnati University Hospital

Cincinnati, Ohio, United States

Site Status

Good Samaritan Hospital

Cincinnati, Ohio, United States

Site Status

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Site Status

Jackson-Madison County General Hospital

Jackson, Tennessee, United States

Site Status

Monroe Carell Jr Children's Hospital at Vanderbilt

Nashville, Tennessee, United States

Site Status

University of Texas, Houston

Houston, Texas, United States

Site Status

Countries

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United States

References

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Maitre NL, Ballard RA, Ellenberg JH, Davis SD, Greenberg JM, Hamvas A, Pryhuber GS; Prematurity and Respiratory Outcomes Program. Respiratory consequences of prematurity: evolution of a diagnosis and development of a comprehensive approach. J Perinatol. 2015 May;35(5):313-321. doi: 10.1038/jp.2015.19. Epub 2015 Mar 26.

Reference Type BACKGROUND
PMID: 25811285 (View on PubMed)

Pryhuber GS, Maitre NL, Ballard RA, Cifelli D, Davis SD, Ellenberg JH, Greenberg JM, Kemp J, Mariani TJ, Panitch H, Ren C, Shaw P, Taussig LM, Hamvas A; Prematurity and Respiratory Outcomes Program Investigators. Prematurity and respiratory outcomes program (PROP): study protocol of a prospective multicenter study of respiratory outcomes of preterm infants in the United States. BMC Pediatr. 2015 Apr 10;15:37. doi: 10.1186/s12887-015-0346-3.

Reference Type BACKGROUND
PMID: 25886363 (View on PubMed)

Poindexter BB, Feng R, Schmidt B, Aschner JL, Ballard RA, Hamvas A, Reynolds AM, Shaw PA, Jobe AH; Prematurity and Respiratory Outcomes Program. Comparisons and Limitations of Current Definitions of Bronchopulmonary Dysplasia for the Prematurity and Respiratory Outcomes Program. Ann Am Thorac Soc. 2015 Dec;12(12):1822-30. doi: 10.1513/AnnalsATS.201504-218OC.

Reference Type BACKGROUND
PMID: 26397992 (View on PubMed)

Dylag AM, Kopin HG, O'Reilly MA, Wang H, Davis SD, Ren CL, Pryhuber GS. Early Neonatal Oxygen Exposure Predicts Pulmonary Morbidity and Functional Deficits at 1 Year. J Pediatr. 2020 Aug;223:20-28.e2. doi: 10.1016/j.jpeds.2020.04.042.

Reference Type DERIVED
PMID: 32711747 (View on PubMed)

Voynow JA, Fisher K, Sunday ME, Cotten CM, Hamvas A, Hendricks-Munoz KD, Poindexter BB, Pryhuber GS, Ren CL, Ryan RM, Sharp JK, Young SP, Zhang H, Greenberg RG, Herring AH, Davis SD. Urine gastrin-releasing peptide in the first week correlates with bronchopulmonary dysplasia and post-prematurity respiratory disease. Pediatr Pulmonol. 2020 Apr;55(4):899-908. doi: 10.1002/ppul.24665. Epub 2020 Jan 29.

Reference Type DERIVED
PMID: 31995668 (View on PubMed)

Ren CL, Feng R, Davis SD, Eichenwald E, Jobe A, Moore PE, Panitch HB, Sharp JK, Kisling J, Clem C, Kemp JS. Tidal Breathing Measurements at Discharge and Clinical Outcomes in Extremely Low Gestational Age Neonates. Ann Am Thorac Soc. 2018 Nov;15(11):1311-1319. doi: 10.1513/AnnalsATS.201802-112OC.

Reference Type DERIVED
PMID: 30088802 (View on PubMed)

Blaisdell CJ, Troendle J, Zajicek A; Prematurity and Respiratory Outcomes Program. Acute Responses to Diuretic Therapy in Extremely Low Gestational Age Newborns: Results from the Prematurity and Respiratory Outcomes Program Cohort Study. J Pediatr. 2018 Jun;197:42-47.e1. doi: 10.1016/j.jpeds.2018.01.066. Epub 2018 Mar 26.

Reference Type DERIVED
PMID: 29599068 (View on PubMed)

Keller RL, Feng R, DeMauro SB, Ferkol T, Hardie W, Rogers EE, Stevens TP, Voynow JA, Bellamy SL, Shaw PA, Moore PE; Prematurity and Respiratory Outcomes Program. Bronchopulmonary Dysplasia and Perinatal Characteristics Predict 1-Year Respiratory Outcomes in Newborns Born at Extremely Low Gestational Age: A Prospective Cohort Study. J Pediatr. 2017 Aug;187:89-97.e3. doi: 10.1016/j.jpeds.2017.04.026. Epub 2017 May 17.

Reference Type DERIVED
PMID: 28528221 (View on PubMed)

Other Identifiers

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U01HL101794-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

813839

Identifier Type: -

Identifier Source: org_study_id