Effects of Prophylactic Desmopressin on Blood Coagulation Parameters in Heart Valve Surgery

Placebo-Controlled, Randomized, Double-Blind Trial of Prophylactic Desmopressin in Heart Valve Surgery

The purpose of this study is evaluate the effect of prophylactic desmopressin on blood coagulation parameters and postoperative bleeding in patients undergoing valve cardiac surgery with cardiopulmonary bypass.

Study Overview

• Status: Unknown
• Conditions: Blood Coagulation Disorders; C.Surgical Procedure; Cardiac
• Intervention / Treatment: Drug: Desmopressin; Drug: Placebo

Detailed Description

Patients with important valve disorders may evaluate with coagulopathy induced by mechanical effects (valvular stenosis or valvular insufficiency). Furthermore, frequently is required prophylactic use of antiplatelet drugs due to myocardial remodeling and antiarrhythmic conditions that may be associated. Patients with severe aortic stenosis may also acquired von Willebrand disease type 2A due to proteolysis of vonWillebrand factor. Despite of this, the treatment of valve disorders often requires cardiac surgery with cardiopulmonary bypass. On average 50 to 60% of patients undergoing cardiac surgery receive blood tranfusions. Blood cell transfusion is an independent risk factor for increased morbidity and mortality in critically ill patients. The use of desmopressin seems beneficial only in patients with congenital or acquired platelet dysfunction. In general population, such use is not validated due to inconclusive results of researches.

• Study Type: Interventional
• Enrollment (Anticipated): 108
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403000
    • Incor - Heart Institute - University of Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Valve cardiac surgery with cardiopulmonary bypass.
• Written informed consent

Exclusion Criteria:

• Reoperative valve surgery
• Hematocrit < 35%
• Ventricular dysfunction (EF < 40%)
• Infection
• Body mass index > 35
• Renal impairment (Creatinin > 2mg/dL)
• Antiplatelet administration within 10 days preceding study surgery
• Participation in another interventional clinical study within 30 days
• Known or suspected hypersensitivity to the desmopressin
• Coagulopathy (INR > 1.5)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: desmopressin; Patients randomized to this group receive desmopressin 0,3 microgram.kg-1 as an intravenous infusion given during 20 min.	Drug: Desmopressin; Desmopressin is to be administered as an intravenous infusion after discontinuation of cardiopulmonary bypass and administration of protamine. Subjects are to be given desmopressin 0,3 microgram.kg-1. After desmopressin infusion, bleeding treatment will follow the predefined standardized treatment regimen.
PLACEBO_COMPARATOR: Placebo; Patients randomized to the control group will receive the infusion of 100 mL 0.9% saline (SF0,9%).	Drug: Placebo; 0.9% saline is to be administered as an intravenous infusion after discontinuation of cardiopulmonary bypass and administration of protamine. Patients randomized to the control group will receive the infusion of 100 milliliters (mL) 0.9% saline (SF0,9%). After 0.9% saline infusion, bleeding treatment will follow the predefined standardized treatment regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in coagulation parameters	Laboratory variables: Activated partial thromboplastin time [(aPTT) seconds], prothrombin time [(PT) seconds], haematocrit (%), haemoglobin(g/dl), fibrinogen(mg/dL), D dimer (ng/L), factor VIII(%), Von Willebrand factor(%), ROTEM [(INTEM, EXTEM, FIBTEM) Clotting Time (CT) and Clot Formation Time (CFT) seconds, alpha angle (α º), Maximum Clot Firmness (MCF) mm ] and platelets aggregation (%)	Coagulation parameters will be performed: T0: preoperative period; T1 - 2 hours after desmopressin or placebo administration; T2 - 24 hours after desmopressin or placebo administration
Postoperative blood loss	Total chest tube drainage (mL) starting immediately after closure of the chest in the operating theater until 48 hours	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		30 days
Length of hospital stay		30 days
Length of ICU stay		30 days
Blood transfusion	Number of units of red blood cells, fresh frozen plasma,platelets, cryoprecipitate in the operating theater and ICU	30 days
Reoperation for bleeding		30 days
Duration of Mechanical ventilation		30 days
Length of vasoactive drugs		30 days
Clinical complications - renal failure, infection, myocardial ischemia, stroke		30 days

Collaborators and Investigators

• Sponsor: Instituto do Coracao

Publications and helpful links

General Publications

• Galas FR, de Almeida JP, Fukushima JT, Vincent JL, Osawa EA, Zeferino S, Camara L, Guimaraes VA, Jatene MB, Hajjar LA. Hemostatic effects of fibrinogen concentrate compared with cryoprecipitate in children after cardiac surgery: a randomized pilot trial. J Thorac Cardiovasc Surg. 2014 Oct;148(4):1647-55. doi: 10.1016/j.jtcvs.2014.04.029. Epub 2014 Apr 18.

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (ANTICIPATED): November 1, 2017
• Study Completion (ANTICIPATED): November 1, 2017

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: November 10, 2017
• First Posted (ACTUAL): November 17, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2017
• Last Update Submitted That Met QC Criteria: November 16, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Bleeding; Desmopressin; Valve Cardiac Surgery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Coagulation Disorders; Physiological Effects of Drugs; Natriuretic Agents; Hemostatics; Coagulants; Antidiuretic Agents; Deamino Arginine Vasopressin
• Other Study ID Numbers: 3962.13.087