Ductus Arteriosus Closure and D-Dimer and Fibrinogen Levels

Ductus Arteriosus, Patent Clinical Trial

Official title:

The Relationship of Ductus Arteriosus Closure and D-Dimer and Fibrinogen Levels in Premature Babies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04508036
• Other study ID #: KA-19033
• Status: Recruiting
• Start date: March 14, 2019
• Est. completion date: December 31, 2023

Study information

• Verified date: February 2023
• Source: Hacettepe University
• Contact: Hasan Tolga Çelik
• Phone: +90 530 592 55 84
• Email: htcelik[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this study is to investigate whether there is a relationship between echocardiographic measurements regarding closure of PDA and serum D-Dimer and Fibrinogen levels in premature infants born before 32nd gestational week and weighing less than 1500 grams.

Description:

Ductus arteriosus (DA) is located between the main pulmonary artery and descending aorta in embryonal life, with dense spiral-located smooth muscle cells in the media layer, and the intima layer is thicker than the aorta. It must be open in fetal life; in this way, the blood flowing from the right ventricle to the collapsed lungs is directed to the descending aorta. DA usually closes "functionally" by constriction of the media during the first three days after labor. In the second week after birth; endothelial folding, subendothelial proliferation and coagulation processes results in "anatomical" permanent closure.

When not closed, patent ductus arteriosus (PDA) is formed resulting in shunting from aorta to pulmonary artery. Probability of patency is inversely related with birth weight. Risk of pulmonary edema, pulmonary hemorrhage, bronchopulmonary dysplasia and loss of pulmonary function increases due to increased pulmonary flow from left to right shunt. Renal, mesenteric and cranial blood supply are impaired due to reduced peripheral circulation. As a result, impaired renal function and necrotizing enterocolitis may develop. Risk of intracranial hemorrhage, cerebral hypoxia and premature retinopathy due to variable blood supply. It has been associated with increased mortality in newborns due to increased morbidity. On physical examination, hyperdynamic precordium, viable pulses and left ventricular hypertrophy are observed. Large PDAs are characterized by prominent pulmonary conus, increased pulmonary vascularization and cardiomegaly on telecardiography.

Diagnosis of PDA is confirmed by echocardiography. Symptomatic PDA treatment and follow-up is mostly followed by echocardiography. Detailed echocardiographic examination can only be performed by a Pediatric Cardiologist, but it is not possible to evaluate DA at any time. It is necessary to benefit from significant changes in specific hematological parameters that may accompany DA closure in order to detect and predict these conditions.

One of the main mechanisms involved in anatomic permanent closure in DA is platelet aggregation and coagulation. To the best of our knowledge, there is no study in the literature investigating whether there is a relationship between Fibrinogen and D-dimer levels and anatomical closure of DA. It is postulated that circulating fibrinogen levels will decrease and D-dimer levels increase as a by-product due to thrombosis in the lumen during DA closure. It is predicted that in infants in whom DA does not close and remain open, fibrinogen levels will be higher and D-dimer levels will be lower than infants in whom DA is closed. It is also suggested that echocardiographic DA measurements will correlate with serum Fibrinogen and D-Dimer levels.

The aim of this study is to investigate whether there is a relationship between echocardiographic measurements regarding closure of PDA and serum D-Dimer and Fibrinogen levels in premature infants born before 32nd gestational week and weighing less than 1500 grams.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Days to 28 Days

Eligibility

Inclusion Criteria:

premature newborns born before 32nd gestational week and weighing less than 1500 grams.

Exclusion Criteria:

Babies with:

• Major congenital anomalies

• Chromosomal anomalies

• Inborn errors of metabolism

• Hypoxic ischemic encephalopathy

• Disseminated intravascular coagulation

• Unstable hemodynamic status

• Severe neonatal sepsis

• Who died in time frame of postnatal 14 days

• Patients who are not volunteered to participate

Related Conditions & MeSH terms

• Ductus Arteriosus, Patent

Intervention

Diagnostic Test:
• Withdrawal of blood samples for D-Dimer
Blood samples are withdrawn at birth via cord blood and at postnatal 3rd and 7th days via umbilical catheter in order to test for D-dimer levels.
• Withdrawal of blood samples for Fibrinogen
Blood samples are withdrawn at birth via cord blood and at postnatal 3rd and 7th days via umbilical catheter in order to test for Fibrinogen levels.
• Echocardiographic Examination
At postnatal 3rd, 7th and 14th days, Ductus Arteriosus will be echocardiographically examined to obtain calculations and confirm status of ductal patency or closure.

Locations

Country	Name	City	State
Turkey	Hacettepe University	Ankara

Sponsors (1)

Lead Sponsor	Collaborator
Hacettepe University

Country where clinical trial is conducted

Turkey, 

References & Publications (2)

Sehgal A, Paul E, Menahem S. Functional echocardiography in staging for ductal disease severity : role in predicting outcomes. Eur J Pediatr. 2013 Feb;172(2):179-84. doi: 10.1007/s00431-012-1851-0. Epub 2012 Oct 11. — View Citation

Tay SP, Cheong SK, Boo NY. Circulating tissue factor, tissue factor pathway inhibitor and D-dimer in umbilical cord blood of normal term neonates and adult plasma. Blood Coagul Fibrinolysis. 2003 Feb;14(2):125-9. doi: 10.1097/00001721-200302000-00002. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rise in D-dimer blood levels during Ductus Arteriosus closure from postnatal day 0 to postnatal 3rd and 7th days	It is postulated that circulating D-dimer levels will increase gradually as a by-product due to thrombosis in the lumen during DA closure from postnatal day 0 to postnatal 3rd and 7th days. It is predicted that D-dimer levels will be lower in infants in whom DA does not close than in infants whom DA is closed. Blood samples are withdrawn accordingly at birth via cord blood and at postnatal 3rd and 7th days via umbilical catheter in order to test for D-dimer levels.	postnatal 0 - 14 days
Primary	Fall in Fibrinogen blood levels during Ductus Arteriosus closure from postnatal day 0 to postnatal 3rd and 7th days	It is postulated that circulating fibrinogen levels will fall gradually due to thrombosis in the lumen during DA closure from postnatal day 0 to postnatal 3rd and 7th days. It is predicted that fibrinogen levels will be higher in infants in whom DA does not close than in infants whom DA is closed. Blood samples are withdrawn accordingly at birth via cord blood and at postnatal 3rd and 7th days via umbilical catheter in order to test for fibrinogen levels.	postnatal 0 - 14 days