Clinical trial NCT06833320: Propranolol Treatment for Postoperative Chylothorax
Official title: A Double-blind, Prospective, Randomized Trial of Propranolol for the Treatment of Postoperative Chylothorax After Open Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Postoperative Chylothorax
Congenital Heart Disease
Open Heart Surgery
Chylothorax
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2025-02-18
Enrollment: 50
Sex: ALL
Minimum age (years): 7
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to propranolol or placebo in a 1:1 ratio
Primary purpose: TREATMENT

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.

Detailed description: This clinical trial will prospectively enroll eligible patients and randomize them to placebo or propranolol (1:1). This study will aim to enroll 50 patients, randomized to 25 placebo and 25 propranolol treatment. After patients have been consented, registered, and screened, they will be entered into the study. Participants will be randomized to placebo or propranolol in a 1:1 ratio. Randomization will be double-blinded, and each enrolled participant will be given a number and receive coded medication from the research pharmacy. Patients may undergo a screening MR lymphangiogram (MRL) prior to starting treatment. The criteria for an MRL will require that no additional sedation be given, and patient or parent/legal guardian consents to an MRL. Thus, only patients who are already sedated, or who will be able to undergo the MRL without sedation, and who opts in to the MRL will be eligible. Propranolol or placebo will be administered for 9 days after reaching the lowest effective goal dose not to exceed 2mg/kg/day, or maximum tolerated dose, after which the study groups will be unmasked.

Participants who have ≥80% reduction in volume of chylothorax drainage after 9 days of treatment and who received propranolol are identified as "responders". They will be taken off the study officially at this point as no more study interventions will be given. They will be tapered off of propranolol gradually as clinically indicated.

Participants who have ≥80% reduction in volume of chylothorax drainage but who received placebo will be the "natural history cohort". This will serve to demonstrate, as baseline, the percentage of participants who naturally resolve their chylothorax without intervention.

Patients who have \<80% reduction in chylothorax drainage and who received propranolol, will be categorized as initial "non-responders". They will be officially taken off the study.

Participants who have \<80% reduction in chylothorax drainage and who received placebo are considered a control group. They will be given propranolol for 9 days as a single-arm, open study and re-evaluated after a 9-day treatment. After 9 days at goal dosing, they will receive the same treatment as the responders and non-responders in the propranolol-treated group.

Eligibility criteria: Inclusion Criteria:

* ≥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
* No hemodynamically unstable bradycardia
* No systolic hypotension not corrected by pressor support
* Not in 2nd or 3rd degree heart block
* No history of asthma
* A parent or a legal guardian must sign a written informed consent and HIPAA Form
* Patients will be required to also be enrolled in a related study (AAAQ6902) which collects chylothorax fluid for cell isolation and genetic analysis

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Daily heart rates recorded in flow chart and 1 hour after each dose
timeFrame: 24 days
measure: Daily blood pressures recorded in flow chart and 1 hour after each dose
timeFrame: 24 days
measure: Daily glucose levels
timeFrame: 24 days
measure: Expected and unexpected AEs, per patient
timeFrame: 24 days
measure: Days with documented chest tube (# days), CXR
timeFrame: 24 days
measure: Initial volume of fluid drained (mL, mL/kg/day)
timeFrame: Day 0
measure: Days hospitalized
timeFrame: 6 months
Secondary outcomes:
measure: Thyroglobulin (TG) lymphocyte count
timeFrame: 24 days
measure: Pre-operative and post-operative echocardiogram anatomic findings for patients with 4-chamber hearts
timeFrame: Pre-operative and up to 24 days
measure: Pre-operative and post-operative echocardiogram anatomic findings for patients with single ventricle (SV) physiology
timeFrame: Pre-operative and up to 24 days
measure: Percent of patients with Type 1 anatomy
timeFrame: Day 0
measure: Percent of patients with Type 2 anatomy
timeFrame: Day 0
measure: Percent of patients with Type 3 anatomy
timeFrame: Day 0
measure: Percent of patients with Type 4 anatomy
timeFrame: Day 0
measure: Serum albumin
timeFrame: 24 days
measure: White Blood Cell (WBC) count
timeFrame: 24 days
measure: C-Reactive Protein (CRP)
timeFrame: 24 days
measure: Immunoglobulin level
timeFrame: 24 days
measure: AT3 titer
timeFrame: 24 days
measure: Protein S titer
timeFrame: 24 days
measure: Protein C titer
timeFrame: 24 days
measure: Hours on bypass during CHD surgery
timeFrame: During surgery
measure: Triglyceride level in chylothorax fluid
timeFrame: 24 days
Other outcomes:
Locations:
city: New York
country: United States
facility: MS CHONY inpatient units, including regular floor units, stepdown units, and ICU
state: New York
Study officials:
affiliation: Columbia University Irving Medical Center/ New York Presbyterian hospital
name: June Wu, MD
role: PRINCIPAL_INVESTIGATOR
References: