Clinical trial NCT02765633: Cangrelor Neonatal PK/PD and Safety Study
Official title: A Prospective, Open-Label, Single-Arm, Multi-Center Study To Assess The Pharmacokinetics/Pharmacodynamics (PK/PD) And Safety Of Different Cangrelor Doses In Neonatal Subjects At Risk Of Thrombosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Partial Obstruction of Systemic to Pulmonary Artery Shunt
Complete Obstruction of Systemic to Pulmonary Artery Shunt
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2016-05-06
Enrollment: 22
Sex: ALL
Minimum age (years): 1
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the PK/PD and safety profile of cangrelor in neonatal participants at risk of thrombosis.


Eligibility criteria: Inclusion criteria:

1. Males and females with congenital heart disease, and ranging in age from birth through 28 days of life
2. Postoperative neonatal cardiac participants with placement of systemic-to-pulmonary artery palliative shunts, right ventricle to pulmonary artery palliative shunts, or ductus arteriosus stents who are at risk of thrombotic events after repair for structural congenital heart disease.
3. Written informed consent from a parent/legal guardian
4. Life expectancy of at least 15 days at study entry

Participants will be excluded from the study if any of the following exclusion criteria apply:

1. History of intracerebral bleed (confirmed by a ultrasound (US) of the head prior to surgery), or cerebral arteriovenous malformation, or any prior bleed with neurological deficit
2. Gastrointestinal or urinary bleeding
3. Cerebrovascular accident or any cerebrovascular accident with a residual neurological deficit
4. Known congenital or acquired bleeding or clotting disorder
5. Weight less than 2.5 kilograms (kg)
6. Adjusted gestational age less than 37 weeks
7. Platelet count less than 100,000 cells/microliter (µL)
8. Chest and/or mediastinal tube blood output of greater than 3 milliliters (mL)/kg/hour (hr) at the time of cangrelor administration
9. Participants with evidence of severe hepatic or renal failure \[aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than three times normal for age or total bilirubin greater than 20 milligrams (mg)/deciliter (dL); creatinine greater than 2 times the normal upper limit\]
10. Known allergy to cangrelor or known sensitivity to any component of cangrelor
11. Any condition that in the investigator's opinion would constitute a contraindication to participation in the study or cause inability to comply with the study requirements
12. Participation in another investigational therapeutic drug or investigational therapeutic device trial within 30 days of starting study
13. Participants who have been receiving warfarin (Coumadin®) therapy

Primary outcomes:
measure: Total plasma concentrations of cangrelor and its primary metabolite, AR C69712, during administration and after cessation of the infusion in neonates
timeFrame: During study drug infusion through 8 hours post infusion
measure: Proportion of participants in each cohort who achieve ≥90% inhibition of final platelet aggregation as measured by light transmittance aggregometry (LTA) using 20 micromolar (µM) adenosine diphosphate (ADP) in platelet rich plasma
timeFrame: During study drug infusion through 1 hour post infusion
measure: Individual recovery of platelet function in neonates after cessation of the infusion
timeFrame: Up to 1 hour post infusion
measure: Assessment of the safety of cangrelor in neonatal participants by evaluating adverse events (AEs) and serious adverse events (SAEs)
timeFrame: from start of cangrelor infusion through 48 hours post cangrelor infusion
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Columbia University
name: Thomas Diacovo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vargas D, Zhou H, Yu X, Diamond S, Yeh J, Allada V, Krishnamurthy G, Price M, Allen B, Alexander J, Schmidhofer J, Kreutzer J, Vincent J, Morell V, Bacha E, Diacovo T. Cangrelor PK/PD analysis in post-operative neonatal cardiac patients at risk for thrombosis. J Thromb Haemost. 2021 Jan;19(1):202-211. doi: 10.1111/jth.15141. Epub 2020 Nov 29.