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Congenital Diaphragmatic HerniaPhase 2NCT02951130

Milrinone in Congenital Diaphragmatic Hernia

A Phase 2 study testing Milrinone in people with Congenital Diaphragmatic Hernia and Persistent Pulmonary Hypertension of the Newborn, run by NICHD Neonatal Research Network at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Infants with congenital diaphragmatic hernia (CDH) usually have pulmonary hypoplasia and persistent pulmonary hypertension of the newborn (PPHN) leading to hypoxemic respiratory failure (HRF). Read more about this study

Who is it for?
Ages 0 to 168 hours
What is being tested?
Milrinone
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
66 participants
Where
19 sitesUnited States
Study dates
24 Oct 2017to 19 May 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 0 to 168 hours
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

None listed.

Who cannot join

  • Infants are ineligible if they meet any of the following criteria:
  • known hypertrophic cardiomyopathy
  • Note 1: infants of diabetic mothers with asymmetric septal hypertrophy can be included as long as there is no evidence of obstruction to left ventricular outflow tract on echocardiogram,
  • Note 2: infants with other acyanotic congenital heart disease (CHD) and CDH may be included in the study and will be a predetermined subgroup for analysis)
  • cyanotic CHD - transposition of great arteries (TGA), total anomalous pulmonary venous return (TAPVR), partial anomalous pulmonary venous return (PAPVR), truncus arteriosus (TA), tetralogy of Fallot (TOF), single ventricle physiology - hypoplastic left heart syndrome (HLHS), tricuspid atresia, critical pulmonic stenosis or atresia etc.,
  • enrolled in conflicting clinical trials (such as a randomized controlled blinded trial of another pulmonary vasodilator therapy); Note: mothers enrolled in fetal tracheal occlusion studies such as FETO may be enrolled if permitted by investigators of the fetal tracheal occlusion study; [FETO refers to fetoscopic endoluminal tracheal occlusion and involves occlusion of fetal trachea with a balloon device at mid-gestation and subsequent removal in later gestation]
Show all 26Show fewer
  • infants with bilateral CDH
  • o Note 3: infants with anterior and central defects are included in the study
  • associated abnormalities of the trachea or esophagus (trachea-esophageal fistula, esophageal atresia, laryngeal web, tracheal agenesis)
  • renal dysfunction (with serum creatinine > 2 mg/dL not due to maternal factors) or severe oligohydramnios associated with renal dysfunction at randomization; renal dysfunction may be secondary to renal anomalies or medical conditions such as acute tubular necrosis
  • severe systemic hypotension (mean blood pressure < 35 mm Hg for at least 2 h with a vasoactive inotrope score of > 30)
  • decision is made to provide comfort/ palliative care and not full treatment
  • Intracranial bleed (including the following findings on the cranial ultrasound)
  • Cerebral parenchymal hemorrhage
  • Blood/echodensity in the ventricle with distension of the ventricle
  • Periventricular hemorrhagic infarction
  • Posterior fossa hemorrhage
  • Cerebellar hemorrhage
  • persistent thrombocytopenia (platelet count < 80,000/mm3) despite blood product administration on the most recent blood draw prior to randomization
  • coagulopathy (PT INR > 1.7) despite blood product administration on the most recent blood draw (if checked - there is no reason to check PT for the purpose of this study)
  • aneuploidy associated with short life span (such as trisomy 13 or 18) will not be included in the study (infants with trisomy 21 can be included in the study)
  • elevated arterial, venous or capillary PCO2 > 80 mmHg in spite of maximal ventilator support (including high frequency ventilation) on the most recent blood gas obtained within 12 hours prior to randomization
  • use of milrinone infusion prior to randomization (the use of other inhaled pulmonary vasodilators such as iNO, inhaled epoprosternol, inhaled PGE1 and oral such as endothelin receptor antagonists is permitted - Note: it is unlikely to be on oral pulmonary vasodilators early in the course of CDH)
  • ongoing therapy with parenteral (intravenous or subcutaneous) pulmonary vasodilators such as IV/SQ prostacyclin analogs (Epoprostenol - Flolan or Treprostinil - Remodulin or PGE1 - Alprostadil) or IV phosphodiesterase 5 inhibitors (sildenafil - Revatio) at the time of randomization. In addition, initiation of therapy with these two classes of parenteral medications during the first 24 hours of study drug initiation is not permitted and will be considered a protocol deviation. The risk of systemic hypotension is high during the first 24 hours of study-drug (milrinone) infusion and hence parenteral administration of other pulmonary vasodilators is avoided to minimize risk of hypotension.
  • Subjects already on ECMO or patients who are being actively considered for ECMO by the neonatal or surgical team
  • attending (neonatal, critical care or surgical) refusal for participation in the trial (including concern about presence of hemodynamic instability)

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • University of New Mexico

    Albuquerque, New Mexico, 87131

  • Emory University

    Atlanta, Georgia, 30303

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Cincinnati Children's Medical Center

    Cincinnati, Ohio, 45267

  • Case Western Reserve University, Rainbow Babies and Children's Hospital

    Cleveland, Ohio, 44106

  • Research Institute at Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75235

  • RTI International

    Durham, North Carolina, 27709

  • Duke University

    Durham, North Carolina, 27710

  • University of Texas Health Science Center at Houston

    Houston, Texas, 77030

  • University of Iowa

    Iowa City, Iowa, 52242

  • Children's Mercy

    Kansas City, Missouri, 64108

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Columbia University

    New York, New York, 10032

  • Stanford University

    Palo Alto, California, 94304

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Brown University, Women & Infants Hospital of Rhode Island

    Providence, Rhode Island, 02905

  • University of Rochester

    Rochester, New York, 14642

  • University of Utah

    Salt Lake City, Utah, 84108

Other trials in United States

About this study

Infants with congenital diaphragmatic hernia (CDH) usually have pulmonary hypoplasia and persistent pulmonary hypertension of the newborn (PPHN) leading to hypoxemic respiratory failure (HRF). Pulmonary hypertension associated with CDH is frequently resistant to conventional pulmonary vasodilator therapy including inhaled nitric oxide (iNO). Increased pulmonary vascular resistance (PVR) can lead to right ventricular overload and dysfunction. In patients with CDH, left ventricular dysfunction, either caused by right ventricular overload or a relative underdevelopment of the left ventricle, is associated with poor prognosis. Milrinone is an intravenous inotrope and lusitrope (enhances cardiac systolic contraction and diastolic relaxation respectively) with pulmonary vasodilator properties and has been shown anecdotally to improve oxygenation in PPHN. Milrinone is commonly used during the management of CDH although no randomized trials have been performed to test its efficacy. Thirty percent of infants with CDH in the Children's Hospital Neonatal Database (CHND) and 22% of late-preterm and term infants with CDH in the Pediatrix database received milrinone. In the recently published VICI trial, 84% of patients with CDH received a vasoactive medication. In the current pilot trial, neonates with an antenatal or postnatal diagnosis of CDH will be randomized to receive milrinone or placebo to establish safety of this medication in CDH and test its efficacy in improving oxygenation.

Read the detailed description

This is a pilot trial to determine if milrinone infusion in neonates ≥ 36 weeks' postmenstrual age (PMA) at birth with CDH would lead to an increase in PaO2 with a corresponding decrease in OI by itself or in conjunction with other pulmonary vasodilators such as iNO at 24 h post-infusion.

Being tested
Milrinone, Placebo (5% Dextrose)
Keywords
CDH, PPHN, HRF
Medical subject headings
Hernias, Diaphragmatic, Congenital, Persistent Fetal Circulation Syndrome, Respiratory Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MilrinoneDrug

    Also called Milrinone Lactate Injection, Primacor

    The study intervention is an intravenous infusion of milrinone or placebo

  • Placebo (5% Dextrose)Drug

    Also called D5W

    The study intervention is an intravenous infusion of milrinone or placebo

Study groups in NCT02951130
Study groupRoleWhat they receive
MilrinoneExperimentalMilrinone infusion at 0.33µg/kg/min. The dose of the study drug will be increased to 0.66 µg/kg/min if oxygenation index (OI) remains ≥ 10 without any evidence of hypotension (as defined by the protocol) two hours after initiation of study drug. Infusion will be continued until the OI decreases to < 7. The maximum duration of study drug infusion is 72 hours.
Receives: Drug: Milrinone
5% dextrose (D5W)Placebo comparatorAn equivalent volume of 5% dextrose (D5W) will be used for infants randomized to the placebo arm.
Receives: Drug: Placebo (5% Dextrose)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Oxygenation Response

    The primary outcome of this study is change in oxygenation from baseline (prior to study drug infusion) to 24 hours after initiation of study drug infusion. Oxygenation is assessed by oxygenation index (OI = mean airway pressure x oxygen concentration in % / PaO2 in mmHg). Oxygen saturation index (OSI = mean airway pressure x oxygen concentration in % / oxygen saturation in %) values were converted to OI values for this measure. Data are presented as OI at 24 hours minus OI at baseline. A negative value indicates improvement in oxygenation. A positive value indicates deterioration in oxygenation.

    Measured: 24 h after initiation of study drug

Secondary outcomes (13)

  1. Oxygenation Response at 48 and 72 h

    Oxygenation index at 48 and 72 h (or OI at the time of initiation of ECMO or immediately prior to death, for infants placed on ECMO or died before these time points)

    Measured: 48 and 72 h after initiation of study drug

  2. Changes in Estimated Systolic Pulmonary Arterial Pressure on Echocardiogram

    Changes in echocardiogram to assess pulmonary arterial pressure (as defined by protocol) between pre-study drug echocardiogram and echocardiogram obtained between 24 and 72 h after starting the study drug. The outcome will be available only for those infants who have a pre-study drug echocardiogram and a second echocardiogram between 24 and 72 hours after initiation of study drug performed for clinical reasons.

    Measured: Prior to initiation of study drug to between 24 and 72 hours after initiation of study drug

  3. Vasoactive Inotrope Score and Systemic Blood Pressure

    Vasoactive Inotrope Score is a quantitative assessment of the degree of therapeutic support required by the patient to maintain adequate perfusion and/or blood pressure.

    Measured: 72 hours after initiation of study drug

  4. Area Under the Curve for Inspired Oxygen

    Area under the curve for inspired oxygen after initiation of the study drug (inspired oxygen and ventilator data from 4 time points per day - every 6 hours will be recorded to calculate area under the curve)

    Measured: After initiation of the study drug at 4 time points per day - every 6 hours x 72 hours or discontinuation of study drug (whichever comes first)

  5. Oxygenation Response to Additional Inotropes or Pulmonary Vasodilators

    If subsequent to the study drug, any additional inotrope or pulmonary vasodilator is used (such as iNO), we will evaluate the oxygenation response to these agents. If inotropes or vasodilators were used prior to the initiation of study drug, similar values will be recorded. The OI and PaO2/ FiO2 ratio prior to at least 30 min after initiation of the inotrope / vasodilator are recorded. The change in OI and PaO2/ FiO2 ratio in response to these agents is evaluated as a continuous variable and arbitrarily classified into responders, partial responders and non-responders

    Measured: Through 24 h post study drug initiation

  6. Supplemental Continuous Oxygen

    The use of supplemental oxygen at 28 d will be used to calculate the incidence of chronic lung disease. Chronic lung disease severity will be classified similar to the BPD classification in preterm infants at > 32 week gestation.

    Measured: 28 days and 56 days postnatal age (or discharge whichever comes first)

  7. Survival to Discharge Without ECMO

    Measured: Measured by no ECMO at time of hospital discharge or at the time the infant reaches 120 days of life and remains in the hospital, whichever comes earlier

  8. Clinical Status (Pulmonary and Nutritional)

    Clinical status - pulmonary (use of supplemental oxygen or respiratory medications - diuretics, methylxanthines, steroids, inhaled or nebulized steroids or bronchodilators) and nutritional (weight, length, head circumference, use of anti-reflux medications)

    Measured: All clinical status measures (as defined by protocol) will be obtained just prior to the infants discharge from the hospital and again at 12 months of age.

  9. Feasibility and Sample Size Calculation to Perform a Definitive Trial (Primary Outcome - Improvement in Survival Without ECMO

    Measured: From initial recruitment: 16 patients enrolled per month to complete the trial in 4 years

  10. Feasibility to Perform a Definitive Trial (Incidence of Systemic Hypotension)

    Measured: From initial recruitment: 16 patients enrolled per month to complete the trial in 4 years

  11. Feasibility to Perform a Definitive Trial (Incidence of Intracranial Bleeding)

    Measured: From initial recruitment: 16 patients enrolled per month to complete the trial in 4 years

  12. Feasibility to Perform a Definitive Trial (Incidence of Arrhythmias)

    Measured: From initial recruitment: 16 patients enrolled per month to complete the trial in 4 years

  13. Adjusted Oxygen Response

    Measured: 24 h after initiation of study drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2016 (estimated)
  2. Study start24 Oct 2017
  3. Primary completion30 Sep 2024
  4. Study completion19 May 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02951130
Sponsor's protocol ID
NICHD-NRN-0057
Other IDs
UG1HD034216, UG1HD027904, UG1HD021364, UG1HD027853, UG1HD040689, UG1HD040492, UG1HD027851, UG1HD087229
Status last verified
Sep 2025
First submitted
14 Oct 2016
Last updated
6 Nov 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Per NIH Data Sharing Plan

Publications

  • Lakshminrusimha S, Keszler M, Kirpalani H, Van Meurs K, Chess P, Ambalavanan N, Yoder B, Fraga MV, Hedrick H, Lally KP, Nelin L, Cotten M, Klein J, Guilford S, Williams A, Chaudhary A, Gantz M, Gabrio J, Chowdhury D, Zaterka-Baxter K, Das A, Higgins RD. Milrinone in congenital diaphragmatic hernia - a randomized pilot trial: study protocol, review of literature and survey of current practices. Matern Health Neonatol Perinatol. 2017 Nov 27;3:27. doi: 10.1186/s40748-017-0066-9. eCollection 2017.

    PubMed 29209510

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Milrinone in people with Congenital Diaphragmatic Hernia and Persistent Pulmonary Hypertension of the Newborn, run by NICHD Neonatal Research Network at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Oxygenation Response (time frame: 24 h after initiation of study drug). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02951130, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2025.

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Milrinone in Congenital Diaphragmatic Hernia | AzTrials