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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
C.Surgical Procedure; Cardiac, Blood Coagulation Disorders

Intervention / Treatment
-----------------
* Drug: Desmopressin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: desmopressin<br>Patients randomized to this group receive desmopressin 0,3 microgram.kg-1 as an intravenous infusion given during 20 min. | Drug: Desmopressin<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Patients randomized to the control group will receive the infusion of 100 mL 0.9% saline (SF0,9%). | Drug: Placebo<br>* 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.<br>|

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 |
| --- | --- | --- |
| 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 | 
| Length of ICU stay |  | 30 days | 
| Clinical complications - renal failure, infection, myocardial ischemia, stroke |  | 30 days | 
| Length of hospital stay |  | 30 days | 
| Mortality |  | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bleeding, Valve Cardiac Surgery, Desmopressin