Severe Aortic Stenosis and Acquired Von Willebrand´s Disease: The Impact of Desmopressin in Valve-Replacement Surgery

Acquired Von Willebrand disease (type 2A) has been described in patients with severe aortic stenosis, the association of aortic stenosis and Digestive bleeding due to this phenomena has received the name of Heye´s syndrome.

We propose that administering Desmopressin (DDAVP) in patients scheduled to aortic valve replacement surgery will reduce blood loss and transfusion rate.

this was a pilot study

Study Overview

• Status: Completed
• Conditions: Severe Aortic Stenosis; Acquired Von Willebrand Disease Secondary to Severe Aortic Stenosis; Heye´s Syndrome
• Intervention / Treatment: Drug: desmopressin

Detailed Description

Randomized Controlled trial compared with placebo in a double blind fashion. Subjects with severe aortic stenosis (transvalvular gradient >50 mmHg or valvular area of lass than 1 cm2) scheduled for aortic valve replacement were enrolled.

the day of surgery blood samples were taken in order to confirm diagnosis (factor VIII activity and Protein electrophoresis for Von Willebrand´s multimers) and then 0,3 mcg/k of DDAVP or saline equally labeled as "study drug" were administered en 30 minutes a half hour before incision.

Blood loss, postoperative hematocrit and transfusion requirement were measured, plasma sodium was measured as a safety issue.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• Chile
  • Region Metropolitana
    • Santiago, Region Metropolitana, Chile
      • Hospital Clínico Universidad Católica de Chile

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• severe aortic stenosis defined as mean transvalvular gradient greater or equal to 40 mmHg ot transvalvular area less than 1 cm2
• scheduled for aortic valve replacement surgery

Exclusion Criteria:

• combined surgery (plus coronary artery bypass graft or other valve replacement/plasty)
• Infective Endocarditis
• previously known haemostatic disorder
• previous treatment with oral anticoagulants or IIb-IIIa inhibitors (we did not exclude those on acetyl-salicylic acid)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Desmopressin; 0,3 mcg per kilogram of desmopressin in 100 ml of saline, labeled as "study drug" and administered in 30 minutes a half hour before surgical incision	Drug: desmopressin; 0.3 mcg per kilogram administered in 30 minutes a half hour previous to surgical incision; Other Names: DDAVP
Placebo Comparator: placebo; 100 of saline labeled as "study drug" administered in 30 minutes a half hour before surgical incision	Drug: desmopressin; 0.3 mcg per kilogram administered in 30 minutes a half hour previous to surgical incision; Other Names: DDAVP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood loss	Blood loss obtained from fluid balance of surgery plus drain output	once patient arrives to post anesthesia care unit (approximately 6 hours after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative hematocrit	hematocrit and hemoglobin in time frame mentioned	the morning after surgery (18-24 hours after drug administration)
need of transfusion	transfusion of packaged red cells units until 48 hours after administration of study drug	48 hours post administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of hyponatremia	blood sampling for plasma sodium in specified time frame	18-24 hours post administration of study drug
von Willebrand study and protein electrophoresis	blood sampling for von Willebrand study: collagen binding activity; ristocetin factor test; coagulation factor VIII activity; von Willebrand factor antigen; Ristocetin cofactor test/von Willebrand factor antigen ratio and protein electrophoresis of von Willebrand multimers	the day of surgery, half hour previous to administration of study drug

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Collaborators: Ferring Pharmaceuticals
• Investigators: Principal Investigator: esperanza carrasco, anesthesiologist, Pontificia Universidad Catolica de Chile; Study Director: rodrigo lopez, anesthesiologist, Pontificia Universidad Catolica de Chile; Study Chair: guillermo lema, profesor titular, Pontificia Universidad Catolica de Chile

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: November 14, 2013
• First Submitted That Met QC Criteria: November 19, 2013
• First Posted (Estimate): November 25, 2013

Study Record Updates

• Last Update Posted (Actual): April 5, 2017
• Last Update Submitted That Met QC Criteria: April 4, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: severe aortic stenosis; desmopressin; acquired von Willebrand disease; Heye´s syndrome; von Willebrand multimers
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Blood Coagulation Disorders; Blood Platelet Disorders; Aortic Valve Stenosis; Constriction, Pathologic; Von Willebrand Diseases; Physiological Effects of Drugs; Natriuretic Agents; Hemostatics; Coagulants; Antidiuretic Agents; Deamino Arginine Vasopressin
• Other Study ID Numbers: RVA