Postoperative ChylothoraxPhase 1/2NCT06833320
Propranolol Treatment for Postoperative Chylothorax
A Phase 1/2 study testing Propranolol Hydrochloride in people with Postoperative Chylothorax and Congenital Heart Disease, run by June Wu at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 7 days to 18 years
- Conditions the study is for
- Postoperative Chylothorax, Congenital Heart Disease, Open Heart Surgery
- What is being tested?
- Propranolol Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Sep 2025to 1 Jan 2031
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 7 days to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- ≥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
Show all 21Show fewer
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center/NewYork-Presbyterian
New York, New York, 10032
About this study
Official title: A Double-blind, Prospective, Randomized Trial of Propranolol for the Treatment of Postoperative Chylothorax After Open Cardiac Surgery
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.
Read the 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.
- Being tested
- Propranolol Hydrochloride, Placebo
- Medical subject headings
- Heart Defects, Congenital, Chylothorax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Propranolol HydrochlorideDrug
Also called Propranolol, 2-Propanol, 1-[(1-methylethyl)amino]-3-(1- naphthalenyloxy)-, hydrochloride
Propranolol will be administered as tablets. Participants who are too young to swallow pills will be given propranolol solution.
PlaceboDrug
Also called Ora-Blend
Placebo suspension will only have Ora-Blend Medication Flavoring and Suspension Vehicle
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo suspension will only have Ora-Blend Receives: 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. Receives: Drug: Propranolol Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Daily heart rates recorded in flow chart and 1 hour after each dose
Safety outcome
Measured: 24 days
Daily blood pressures recorded in flow chart and 1 hour after each dose
Safety outcome
Measured: 24 days
Daily glucose levels
Safety outcome
Measured: 24 days
Expected and unexpected AEs, per patient
Safety outcome
Measured: 24 days
Days with documented chest tube (# days), CXR
Will also measure the daily output (volume) in the chest tube(s)
Measured: 24 days
Initial volume of fluid drained (mL, mL/kg/day)
The volume at the initial day of postoperative chylothorax diagnosis
Measured: Day 0
Days hospitalized
The length of hospital stay, from post-surgery to discharge
Measured: 6 months
Secondary outcomes (16)
Thyroglobulin (TG) lymphocyte count
The TG count will be analyzed from the postoperative chylothorax fluid.
Measured: 24 days
Pre-operative and post-operative echocardiogram anatomic findings for patients with 4-chamber hearts
This outcome will be reported as the percent of patients with normal LV function, normal RV function, and normal pulmonary artery pressure.
Measured: Pre-operative and up to 24 days
Pre-operative and post-operative echocardiogram anatomic findings for patients with single ventricle (SV) physiology
This outcome will be reported as the percent of patients with normal ventricular function and normal pulmonary artery pressure.
Measured: Pre-operative and up to 24 days
Percent of patients with Type 1 anatomy
Screening MR lymphangiogram: An optional imaging study to define lymphatic anatomy subtype
Measured: Day 0
Percent of patients with Type 2 anatomy
Screening MR lymphangiogram: An optional imaging study to define lymphatic anatomy subtype
Measured: Day 0
Percent of patients with Type 3 anatomy
Screening MR lymphangiogram: An optional imaging study to define lymphatic anatomy subtype
Measured: Day 0
Percent of patients with Type 4 anatomy
Screening MR lymphangiogram: An optional imaging study to define lymphatic anatomy subtype
Measured: Day 0
Serum albumin
to be extracted from clinical lab results, if available
Measured: 24 days
White Blood Cell (WBC) count
to be extracted from clinical lab results, if available
Measured: 24 days
C-Reactive Protein (CRP)
to be extracted from clinical lab results, if available
Measured: 24 days
Immunoglobulin level
to be extracted from clinical lab results, if available
Measured: 24 days
AT3 titer
to be extracted from clinical lab results, if available
Measured: 24 days
Protein S titer
to be extracted from clinical lab results, if available
Measured: 24 days
Protein C titer
to be extracted from clinical lab results, if available
Measured: 24 days
Hours on bypass during CHD surgery
The amount of time the participant was on bypass during heart surgery
Measured: During surgery
Triglyceride level in chylothorax fluid
Triglyceride levels will be measured
Measured: 24 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2025
- Study start9 Sep 2025
- Primary completion30 Sep 2028 (estimated)
- Study completion1 Jan 2031 (estimated)
Why it stopped: Administrative changes
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postoperative ChylothoraxStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to propranolol or placebo in a 1:1 ratio
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- June Wu
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor-investigator, June Wu, Columbia University
- Investigators
- June Wu, MD, Principal investigator, Columbia University Irving Medical Center/ New York Presbyterian hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06833320
- Sponsor's protocol ID
- AAAV5303
- Status last verified
- May 2026
- First submitted
- 18 Dec 2024
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The aggregate data can be shared. The plan is not to share individual participant data to protect their privacy.
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Prospective, Randomized Trial of Propranolol for the Treatment of Postoperative Chylothorax After Open Cardiac Surgery
- ClinicalTrials.gov ID
- NCT06833320
- Acronym / sponsor ID
- AAAV5303
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Administrative changes
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- June WuUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 9 Sep 2025 (actual)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 1 Jan 2031 (estimated)
- First posted
- 18 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Participants will be randomized to propranolol or placebo in a 1:1 ratio
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo suspension will only have Ora-Blend |
| Propranolol hydrochloride | Active comparator | Drug: Propranolol HydrochlorideSubjects 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. |
Who may qualify
- Ages
- 7 days to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- ≥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
Key exclusion criteria (8 listed)
- Pregnancy
- Renal failure at time of enrollment
- Hypotension despite pressor support
- Unstable bradycardia without capacity for pacing
- History of asthma or chronic bronchodilator therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Propranolol HydrochlorideAlso: Propranolol, 2-Propanol, 1-[(1-methylethyl)amino]-3-(1- naphthalenyloxy)-, hydrochloridePropranolol will be administered as tablets. Participants who are too young to swallow pills will be given propranolol solution. | Drug | Propranolol hydrochloride |
| PlaceboAlso: Ora-BlendPlacebo suspension will only have Ora-Blend Medication Flavoring and Suspension Vehicle | Drug | Placebo |
Primary outcome
Daily heart rates recorded in flow chart and 1 hour after each dose
Time frame: 24 days
Safety outcome
Daily blood pressures recorded in flow chart and 1 hour after each dose
Time frame: 24 days
Safety outcome
Daily glucose levels
Time frame: 24 days
Safety outcome
Expected and unexpected AEs, per patient
Time frame: 24 days
Safety outcome
Days with documented chest tube (# days), CXR
Time frame: 24 days
Will also measure the daily output (volume) in the chest tube(s)
Initial volume of fluid drained (mL, mL/kg/day)
Time frame: Day 0
The volume at the initial day of postoperative chylothorax diagnosis
Days hospitalized
Time frame: 6 months
The length of hospital stay, from post-surgery to discharge
16 secondary outcomes
Thyroglobulin (TG) lymphocyte count
Time frame: 24 days
Pre-operative and post-operative echocardiogram anatomic findings for patients with 4-chamber hearts
Time frame: Pre-operative and up to 24 days
Pre-operative and post-operative echocardiogram anatomic findings for patients with single ventricle (SV) physiology
Time frame: Pre-operative and up to 24 days
Percent of patients with Type 1 anatomy
Time frame: Day 0
Percent of patients with Type 2 anatomy
Time frame: Day 0
Percent of patients with Type 3 anatomy
Time frame: Day 0
Percent of patients with Type 4 anatomy
Time frame: Day 0
Serum albumin
Time frame: 24 days
White Blood Cell (WBC) count
Time frame: 24 days
C-Reactive Protein (CRP)
Time frame: 24 days
Immunoglobulin level
Time frame: 24 days
AT3 titer
Time frame: 24 days
Protein S titer
Time frame: 24 days
Protein C titer
Time frame: 24 days
Hours on bypass during CHD surgery
Time frame: During surgery
Triglyceride level in chylothorax fluid
Time frame: 24 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- 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 deathLink provided by the sponsor.
- Postoperative chylothorax is associated with high resource utilization (prolonged hospitalization and mechanical ventilatory support).Link provided by the sponsor.
- postoperative chlyothorax is associated with increased hospital stay, costs, and mortality.Link provided by the sponsor.
- A review on postoperative chylothorax and lymphatic leakage.Link provided by the sponsor.
- 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).Link provided by the sponsor.
- Individual participant dataSharing planned: No. The aggregate data can be shared. The plan is not to share individual participant data to protect their privacy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
June Wu, MD principal investigator
Columbia University Irving Medical Center/ New York Presbyterian hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Propranolol Hydrochloride in people with Postoperative Chylothorax and Congenital Heart Disease, run by June Wu at 1 site 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 21 inclusion and 8 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: paused, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
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?
Daily heart rates recorded in flow chart and 1 hour after each dose (time frame: 24 days). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 May 2026.