Propranolol Treatment for Postoperative Chylothorax

NCT06833320 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AAAV5303
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Postoperative chylothorax is a serious complication after open heart surgery for pediatric patients with congenital heart disease (CHD). While it was thought to be mechanical injury to the thoracic duct, recent research demonstrated that there are intrinsically abnormal lung lymphatics in CHD patients, and after open heart surgery, the fluid shifts that occur overwhelms these abnormal lung lymphatics. As a result, postoperative chylothorax occurs. Propranolol has been found to be helpful in resolving postoperative chylothorax very quickly (9 days) in a subset of postoperative chylothorax patients (60%). However, it is not known why some patients respond and some do not. The investigators hypothesize that propranolol is safe to use in this patient population, and that certain clinical factors will predict propranolol response, but more importantly, some clinical factors can be optimize to allow more patients with postoperative chylothorax to respond to and benefit from propranolol. In order to improve the understanding of how propranolol works and to maximize benefit to patients, the investigators propose to perform a prospective, randomized, double-blind clinical trial to learn how to best use propranolol in patients with postoperative chylothorax.

Conditions

Postoperative Chylothorax; Congenital Heart Disease; Open Heart Surgery; Chylothorax

Outcome Measures

Primary Outcomes (7)

• Daily heart rates recorded in flow chart and 1 hour after each dose

  Safety outcome

  24 days

• Daily blood pressures recorded in flow chart and 1 hour after each dose

  Safety outcome

  24 days

• Daily glucose levels

  Safety outcome

  24 days

• Expected and unexpected AEs, per patient

  Safety outcome

  24 days

• Days with documented chest tube (# days), CXR

  Will also measure the daily output (volume) in the chest tube(s)

  24 days

• Initial volume of fluid drained (mL, mL/kg/day)

  The volume at the initial day of postoperative chylothorax diagnosis

  Day 0

• Days hospitalized

  The length of hospital stay, from post-surgery to discharge

  6 months

Secondary Outcomes (16)

• Thyroglobulin (TG) lymphocyte count

  24 days

• Pre-operative and post-operative echocardiogram anatomic findings for patients with 4-chamber hearts

  Pre-operative and up to 24 days

• Pre-operative and post-operative echocardiogram anatomic findings for patients with single ventricle (SV) physiology

  Pre-operative and up to 24 days

• Percent of patients with Type 1 anatomy

  Day 0

• Percent of patients with Type 2 anatomy

  Day 0

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo suspension will only have Ora-Blend

Drug: Placebo

Propranolol hydrochloride

ACTIVE COMPARATOR

Subjects will be randomized to receive 2mg/kg/day. Propranolol will be administered orally, either as a tablet or as a solution, in equal divided doses three times a day.

Drug: Propranolol Hydrochloride

Interventions

Propranolol Hydrochloride DRUG

Propranolol will be administered as tablets. Participants who are too young to swallow pills will be given propranolol solution.

Also known as: Propranolol, 2-Propanol, 1-[(1-methylethyl)amino]-3-(1- naphthalenyloxy)-, hydrochloride

Propranolol hydrochloride

Placebo DRUG

Placebo suspension will only have Ora-Blend Medication Flavoring and Suspension Vehicle

Also known as: Ora-Blend

Placebo

Eligibility Criteria

• Age: 7 Days - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ≥7 days and ≤18 years old at time of original cardiac surgery
• Congenital structural cardiac anomaly necessitating surgical correction. Examples include but are not limited to: ASD, VSD, single ventricles, HLHS, Tetralogy of Fallot, transposition of great vessels, AV canal, heart transplant
• developed high output postoperative chylothorax (≥10mL/kg/day), or
• persistent chylous drainage at any volume for ≥7 days after open heart surgery for a congenital cardiac defect
• ≥70% lymphocytes, or
• pleural triglyeride (TG) ≥ half of serum TG, or chylomicron positive
• for patients with lower than normal serum lymphocyte count (agedependent), ≥60% lymphocytes in pleural fluids
• Must have measurable output (chylothorax output in mL)
• Any level of respiratory support (room air, supplemental oxygen, CPAP/BIPAP, ventilatory support)
• Any level of inpatient support (ICUs, step-down units, floor)
• Study participants can be on concomitant treatment for postoperative chylothorax started prior to study initiation
• Study participants can continue on on-going treatment for their primary cardiac other medical conditions
• Study participants can initiate new treatments for their primary cardiac or other medical conditions during trial period
• Adequate renal function
• Not on dialysis

You may not qualify if:

• Pregnancy
• Renal failure at time of enrollment
• Hypotension despite pressor support
• Unstable bradycardia without capacity for pacing
• History of asthma or chronic bronchodilator therapy
• Uncontrolled hypoglycemia or hyperglycemia as per investigators' judgment
• Study participant will be removed from study if they failed 2 consecutive attempts to initiate propranolol (\>10% drop in BP/HR from age-adjusted normative range)
• Study participant experiences ≥ Grade 3 AE (SAE)

Sponsors & Collaborators

• June Wu: lead
• United States Department of Defense: collaborator

Study Sites (1)

Columbia University Irving Medical Center/NewYork-Presbyterian

New York, New York, 10032, United States

RECRUITING

Related Links

• This study demonstrated the risk of developing postoperative chylothorax after open heart surgery, and that developing of this complication leads to prolonged hospitalization/ICU stay, need for mechanical ventilatory support, and death
• Postoperative chylothorax is associated with high resource utilization (prolonged hospitalization and mechanical ventilatory support).
• postoperative chlyothorax is associated with increased hospital stay, costs, and mortality.
• A review on postoperative chylothorax and lymphatic leakage.
• Our clinical study showing a subset of patients responded to propranolol with improved outcomes (shorter hospital stays, shorter days with chest tubes, less infection/thrombus risks).

MeSH Terms

Conditions

Heart Defects, Congenital; Chylothorax

Interventions

Propranolol; 2-Propanol

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pleural Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• June Wu, MD

  Columbia University Irving Medical Center/ New York Presbyterian hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

June Wu, MD

CONTACT

212-342-3704; jw92@cumc.columbia.edu

Shannon Brackett, NP

CONTACT

212-342-3704; snb2163@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Surgery

Model Details: Participants will be randomized to propranolol or placebo in a 1:1 ratio

Study Record Dates

• First Submitted: December 18, 2024
• First Posted: February 18, 2025
• Study Start: September 9, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): January 1, 2031
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)