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| ID | Type | Description | Link |
|---|---|---|---|
| U01HL094338 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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The purpose of this study is to determine if late doses of Infasurf surfactant given when patients are receiving inhaled nitric oxide will interact to improve surfactant function and increase survival without BPD in treated infants.
This is a multi-center, blinded, randomized controlled clinical trial to evaluate the effects of booster doses of exogenous surfactant (Infasurf®, calfactant) in addition to inhaled nitric oxide (iNO) on the outcome of survival without bronchopulmonary dysplasia (BPD, or chronic lung disease of prematurity, characterized by chronic lung dysfunction) at 36 weeks' post-menstrual age (PMA) in extremely low gestational age (ELGAN) infants that are at high risk of the development of BPD. This multi-center trial, with a planned enrollment of 524 infants, will also enable us to evaluate for any adverse effects of late surfactant treatment on short- and long-term outcomes, as we will be collecting data on effects of dosing of late surfactant, co-morbidities of prematurity and neurodevelopmental and pulmonary outcome at 1 year and 24 months corrected age. In addition, we will collect biological specimens for evaluation of the effects of late surfactant replacement therapy (administered as described in this trial) on surfactant function and inflammatory markers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Infasurf surfactant (ONY, Inc.) | Active Comparator | Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, 2, 4, 6 and 8. |
|
| Sham (No Treatment) | Sham Comparator | Infants already receiving inhaled nitric oxide will receive "Sham (no treatment)" doses on study days 0,2,4,6, and 8. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Infasurf surfactant (ONY, Inc.) | Drug | Late doses of Infasurf 3ml/kg will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Survival Without BPD at 36 Weeks Post Menstrual Age. | BPD was diagnosed as need for respiratory support with either positive pressure and/or oxygen as evaluated by physiological oxygen/flow reduction. | 36 weeks post menstrual age +/- 1 week |
| Measure | Description | Time Frame |
|---|---|---|
| Survival Without BPD at 40 Weeks | BPD was diagnosed as need for respiratory support with either positive pressure and/or oxygen as evaluated by physiological oxygen/flow reduction. | 40 weeks PMA +/- 1 week |
| Respiratory Outcomes of TOLSURF Infants at 1 Year Corrected Age |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Roberta A Ballard, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arkansas - Arkansas Childrens Hospital | Little Rock | Arkansas | 72202 | United States | ||
| Alta Bates Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16870913 | Background | Ballard RA, Truog WE, Cnaan A, Martin RJ, Ballard PL, Merrill JD, Walsh MC, Durand DJ, Mayock DE, Eichenwald EC, Null DR, Hudak ML, Puri AR, Golombek SG, Courtney SE, Stewart DL, Welty SE, Phibbs RH, Hibbs AM, Luan X, Wadlinger SR, Asselin JM, Coburn CE; NO CLD Study Group. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med. 2006 Jul 27;355(4):343-53. doi: 10.1056/NEJMoa061088. | |
| 17671061 | Background |
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| ID | Title | Description |
|---|---|---|
| FG000 | Infasurf Surfactant (ONY, Inc.) | Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, 2, 4, 6 and 8. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, 2, 4, 6 and 8. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| Sham (No Treatment) | Drug | Late doses of Sham (No treatment) will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated. |
|
|
Evaluation of respiratory outcome through the first 12 months after birth. questionnaires were administered by phone at 3,6,9 and 12 months to determine respiratory resource use (medications, home support, and hospitalization) No Pulmonary Morbidity (NoPM) was reported for infants who had no resource use in any quarter and Persistent PM was reported for infants having resource use in 3 or 4 quarters. |
| 1 year |
| Pulmonary Outcomes Through 2 Years of Age | Evaluation of pulmonary outcome at 24 months of age. Evaluation of persistent wheezing based on reported wheezing during both first and second year of life. | 2 years |
| Percentage of Participants With Neurodevelopmental Impairment (NDI) at 2 Years. | At 24 months corrected age, children underwent neuropsychological testing with the Bayley Scales of Infant Development-Third Edition (Bayley-3), and composite cognitive, language, and motor scores were collected as well as subscale scores in receptive and expressive speech and fine and gross motor. Infants with greater than one impairment as identified by testing were classified as having neurodevelopmental impairment. | 2 years |
| Berkeley |
| California |
| 94705 |
| United States |
| Oakland Children's Hospital | Oakland | California | 94609 | United States |
| University of California, San Francisco | San Francisco | California | 94143 | United States |
| Wolfson Children's Hospital and Shands HospitaL | Jacksonville | Florida | 32207 | United States |
| Florida Hospital for Children | Orlando | Florida | 32803 | United States |
| All Children's Hospital | St. Petersburg | Florida | 33701 | United States |
| Northwestern Memorial Hospital | Chicago | Illinois | 60611 | United States |
| Children's Memorial Hospital | Chicago | Illinois | 60614 | United States |
| Childrens Hospital and Clinics of Minnesota- Minneapolis | Minneapolis | Minnesota | 55404 | United States |
| University of Minnesota Medical School | Minneapolis | Minnesota | 55455 | United States |
| Children's Hospital and Clinics of Minnesota - St Paul | Saint Paul | Minnesota | 55102 | United States |
| Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| Women's and Children's Hospital of Buffalo | Buffalo | New York | 14222 | United States |
| Stony Brook University Medical Center | Stony Brook | New York | 11794 | United States |
| Wake Forest University- Forsyth Hospital and Brenner Hospital | Winston-Salem | North Carolina | 27103 | United States |
| Medical University of South Carolina(MUSC) | Charleston | South Carolina | 29403 | United States |
| UT Memphis- Memphis Medical Center | Memphis | Tennessee | 38103-2807 | United States |
| UT Houston Health Science Center | Houston | Texas | 77030-1503 | United States |
| Texas Children's Hospital | Houston | Texas | 77030 | United States |
| University of Washington, Seattle | Seattle | Washington | 98195-6320 | United States |
| Ballard PL, Merrill JD, Truog WE, Godinez RI, Godinez MH, McDevitt TM, Ning Y, Golombek SG, Parton LA, Luan X, Cnaan A, Ballard RA. Surfactant function and composition in premature infants treated with inhaled nitric oxide. Pediatrics. 2007 Aug;120(2):346-53. doi: 10.1542/peds.2007-0095. |
| 17403837 | Background | Truog WE, Ballard PL, Norberg M, Golombek S, Savani RC, Merrill JD, Parton LA, Cnaan A, Luan X, Ballard RA; Nitric Oxide (to Prevent) Chronic Lung Disease Study Investigators. Inflammatory markers and mediators in tracheal fluid of premature infants treated with inhaled nitric oxide. Pediatrics. 2007 Apr;119(4):670-8. doi: 10.1542/peds.2006-2683. |
| 26500107 | Result | Ballard RA, Keller RL, Black DM, Ballard PL, Merrill JD, Eichenwald EC, Truog WE, Mammel MC, Steinhorn RH, Rogers EE, Ryan RM, Durand DJ, Asselin JM, Bendel CM, Bendel-Stenzel EM, Courtney SE, Dhanireddy R, Hudak ML, Koch FR, Mayock DE, McKay VJ, O'Shea TM, Porta NF, Wadhawan R, Palermo L; TOLSURF Study Group. Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide. J Pediatr. 2016 Jan;168:23-29.e4. doi: 10.1016/j.jpeds.2015.09.031. Epub 2015 Oct 21. |
| 29627188 | Result | Wai KC, Hibbs AM, Steurer MA, Black DM, Asselin JM, Eichenwald EC, Ballard PL, Ballard RA, Keller RL; Trial of Late Surfactant (TOLSURF) Study Group. Maternal Black Race and Persistent Wheezing Illness in Former Extremely Low Gestational Age Newborns: Secondary Analysis of a Randomized Trial. J Pediatr. 2018 Jul;198:201-208.e3. doi: 10.1016/j.jpeds.2018.02.032. Epub 2018 Apr 4. |
| 28100402 | Result | Keller RL, Eichenwald EC, Hibbs AM, Rogers EE, Wai KC, Black DM, Ballard PL, Asselin JM, Truog WE, Merrill JD, Mammel MC, Steinhorn RH, Ryan RM, Durand DJ, Bendel CM, Bendel-Stenzel EM, Courtney SE, Dhanireddy R, Hudak ML, Koch FR, Mayock DE, McKay VJ, Helderman J, Porta NF, Wadhawan R, Palermo L, Ballard RA; TOLSURF Study Group. The Randomized, Controlled Trial of Late Surfactant: Effects on Respiratory Outcomes at 1-Year Corrected Age. J Pediatr. 2017 Apr;183:19-25.e2. doi: 10.1016/j.jpeds.2016.12.059. Epub 2017 Jan 16. |
| 27583380 | Derived | Wai KC, Keller RL, Lusk LA, Ballard RA, Chan DK; Trial of Late Surfactant (TOLSURF) Study Group. Characteristics of Extremely Low Gestational Age Newborns Undergoing Tracheotomy: A Secondary Analysis of the Trial of Late Surfactant Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2017 Jan 1;143(1):13-19. doi: 10.1001/jamaoto.2016.2428. |
| Sham |
Infants already receiving inhaled nitric oxide will not receive additional doses of late surfactant (Infasurf). |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Infasurf Surfactant (ONY, Inc.) | Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, 2, 4, 6 and 8. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, 2, 4, 6 and 8. |
| BG001 | Sham | Infants already receiving inhaled nitric oxide will not receive additional doses of late surfactant (Infasurf). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | weeks |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Respiratory Severity Score (RSS) - MAP x FiO2 | Respiratory Severity Score (RSS) equals the mean airway pressure (on ventilator or Nasal CPAP) X fraction of inspired oxygen (FiO2). Range can be 0 - 16, higher scores indicating greater disease severity. | Mean | Standard Deviation | score on a scale |
| ||||||||||||||
| Birthweight | Mean | Standard Deviation | grams |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Survival Without BPD at 36 Weeks Post Menstrual Age. | BPD was diagnosed as need for respiratory support with either positive pressure and/or oxygen as evaluated by physiological oxygen/flow reduction. | Posted | Count of Participants | Participants | 36 weeks post menstrual age +/- 1 week |
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| Secondary | Survival Without BPD at 40 Weeks | BPD was diagnosed as need for respiratory support with either positive pressure and/or oxygen as evaluated by physiological oxygen/flow reduction. | Infants who were No BPD at 36 wk were imputed to be No BPD at 40 wk. Infants discharged on oxygen without a challenge test were assigned Yes BPD. | Posted | Count of Participants | Participants | 40 weeks PMA +/- 1 week |
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| Secondary | Respiratory Outcomes of TOLSURF Infants at 1 Year Corrected Age | Evaluation of respiratory outcome through the first 12 months after birth. questionnaires were administered by phone at 3,6,9 and 12 months to determine respiratory resource use (medications, home support, and hospitalization) No Pulmonary Morbidity (NoPM) was reported for infants who had no resource use in any quarter and Persistent PM was reported for infants having resource use in 3 or 4 quarters. | Infants who survived to discharge and had data from questionaires available | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Pulmonary Outcomes Through 2 Years of Age | Evaluation of pulmonary outcome at 24 months of age. Evaluation of persistent wheezing based on reported wheezing during both first and second year of life. | Posted | Count of Participants | Participants | 2 years |
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| Secondary | Percentage of Participants With Neurodevelopmental Impairment (NDI) at 2 Years. | At 24 months corrected age, children underwent neuropsychological testing with the Bayley Scales of Infant Development-Third Edition (Bayley-3), and composite cognitive, language, and motor scores were collected as well as subscale scores in receptive and expressive speech and fine and gross motor. Infants with greater than one impairment as identified by testing were classified as having neurodevelopmental impairment. | Neurodevelopmental testing occurred with only 322 participants. | Posted | Number | percentage of participants | 2 years |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Infasurf Surfactant (ONY, Inc.) | Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, 2, 4, 6 and 8. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated. | 29 | 252 | 29 | 252 | 141 | 252 |
| EG001 | Sham (No Treatment) | Infants already receiving inhaled nitric oxide will receive "Sham (no treatment)" doses on study days 0,2,4,6, and 8. Sham (No Treatment): Late doses of Sham (No treatment) will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated. | 24 | 259 | 24 | 259 | 153 | 259 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | Investigations | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| IVH New or Worsened | General disorders | Systematic Assessment | Evaluation of new or worsened IVH after enrollment. |
| |
| PDA Requiring Treatment | Cardiac disorders | Systematic Assessment | Incidence of infants who's PDA worsened to the point of needing treatment. |
| |
| NEC | Gastrointestinal disorders | Systematic Assessment | Incidence of new or worsened NEC after enrollment. |
| |
| Sepsis | Infections and infestations | Systematic Assessment | Incidence new episodes of culture proven sepsis after enrollment. |
| |
| ROP Class 4-5 or surgery | Eye disorders | Systematic Assessment |
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Possible limitations of the trial: Infants 1) may not have had enough surfactant dysfunction to benefit from replacement; or 2) had irreversible lung damage prior to enrollment; or 3) The dose/frequency of replacement surfactant was inadequate.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Roberta A Ballard, MD | University of California, San Francisco | 415-476-4193 | roberta.ballard@ucsf.edu |
| ID | Term |
|---|---|
| D001997 | Bronchopulmonary Dysplasia |
| D047928 | Premature Birth |
| C580477 | Surfactant Dysfunction |
| ID | Term |
|---|---|
| D055397 | Ventilator-Induced Lung Injury |
| D055370 | Lung Injury |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007235 | Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D013812 | Therapeutics |
| C005703 | salicylhydroxamic acid |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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