Decreasing Hemorrhage Risk in Children With Alagille Syndrome

Novel Protocol to Decrease Peri-procedural and Intra-operative Hemorrhage in Children With Alagille Syndrome

The goal of this interventional study is to test a hemostasis screening protocol and cardiac peri-procedural and post-operative hemostasis pathway to improving bleeding complications and improve patient survival for children with Alagille syndrome and complex cardiac conditions. The main questions it aims to answer are:

• Are children with Alagille syndrome with cardiac anomalies more likely to have acquired von Willebrand syndrome (a condition that causes increased bleeding)
• Does implementation of a novel screening protocol to detect pre-operative bleeding conditions decrease intra-operative and/or post-operative bleeding complications and mortality risk?
• Does implementation of a novel screening protocol to detect and treat bleeding conditions cause thrombotic complications?

Participants will undergo additional hematology and bleeding disorder screening prior to cardiac surgery. They will additionally undergo a detailed family screening for a history of bleeding by a genetic counselor.

Researchers will compare these findings with children who have similar complex cardiac conditions requiring surgery, but who do not have Alagille syndrome to see if bleeding conditions and complications are more or less common in children with Alagille syndrome.

Study Overview

• Status: Enrolling by invitation
• Conditions: Alagille Syndrome; Acquired Von Willebrand Disease; Pulmonary Artery Stenoses
• Intervention / Treatment: Other: Assessment for bleeding disorder with tailored post-operative care

Detailed Description

This study aims to develop and implement a pre-operative screening protocol prior to major procedures or surgeries for children with Alagille syndrome, including cardiac catheterization and cardiothoracic surgery (pulmonary artery reconstruction).

Secondary Objectives

1. Develop and implement an intra-operative protocol for children with Alagille syndrome and acquired von willebrand syndrome.
2. Compare cardiac intra- and up to 48 hour post-operative bleeding complications, post-operative thrombotic complications within 30 days of surgery, and mortality for (a) children with Alagille syndrome with and without acquired von willebrand syndrome, and (b) children without Alagille syndrome.

This is a single-site study with the goal to enroll 40 patients over the course of the study period. All patients that are referred for Pulmonary Artery Reconstruction will be screened for eligibility. All patients will undergo standard of care pre-operative hematologic screening to evaluate for bleeding disorders (specifically platelet aggregation disorders and acquired von Willebrand Factor deficiency).

The study includes a pre-screening period of up to 4 weeks followed by a 12-months follow-up period as part of the standard of care following pulmonary artery reconstruction surgery for children with Alagille syndrome and a research related protocol for children without Alagille syndrome.

Patients would have blood drawn one time at least 2 weeks in advance of their cardiothoracic surgery. This is the screening protocol to understand if they have a bleeding disorder that would change their management in the operating room and after their surgery. For patients that are found to have a bleeding disorder requiring treatment, they would need post-operatively a blood test daily for up to 7 days total and another blood test weekly for 2 weeks and then once prior to discharge.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 0-17 years old
• with complex cardiac condition requiring pulmonary artery reconstruction (branch pulmonary artery stenosis, MAPCAs or Tetralogy of Fallot without MAPCAs)

Exclusion Criteria:

• history of known bleeding disorder
• aged 18 years or older

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alagille syndrome; Patients with complex cardiac conditions requiring cardiothoracic surgery who also have a history of Alagille syndrome.	Other: Assessment for bleeding disorder with tailored post-operative care; Intervention will be expanded lab work-up for hematologic conditions, consultation by Hematology and tailored intra-operative and post-operative plan with aim to mitigate bleeding and hemorrhage risk, balancing thrombotic risk with this intervention.
Experimental: No history of Alagille syndrome; Patients with complex cardiac conditions requiring cardiothoracic surgery who do not have a diagnosis of Alagille syndrome.	Other: Assessment for bleeding disorder with tailored post-operative care; Intervention will be expanded lab work-up for hematologic conditions, consultation by Hematology and tailored intra-operative and post-operative plan with aim to mitigate bleeding and hemorrhage risk, balancing thrombotic risk with this intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood product volume	Intra-operatively through 24 hours post-operatively
Chest tube output blood volume	Intra-operatively through 24 hours post-operatively
Number of participants with pulmonary hemorrhage	Intra-operatively through 24 hours post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of thromboembolism events in patients with hematologic condition	This outcome is to evaluate thrombosis risk for patients identified to have a hematologic condition who receive medication intra-operatively and post-operatively to decrease their risk of bleeding. Occurrence of thromboembolism (including blood vessel, intracardiac, stroke, mediastinal thrombosis events) will be assessed based on imaging.	Intra-operatively through 30 days post-operatively

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Alagille Syndrome Alliance
• Investigators: Principal Investigator: Noelle Ebel, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2023
• Primary Completion (Anticipated): November 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: April 26, 2023
• First Submitted That Met QC Criteria: May 4, 2023
• First Posted (Estimate): May 8, 2023

Study Record Updates

• Last Update Posted (Estimate): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Disease; Congenital Abnormalities; Hematologic Diseases; Liver Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Blood Platelet Disorders; Biliary Tract Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Abnormalities, Multiple; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Syndrome; Hemorrhage; Von Willebrand Diseases; Stenosis, Pulmonary Artery; Alagille Syndrome
• Other Study ID Numbers: 66477

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No