Viewing Study NCT03598907



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Last Modification Date: 2024-10-26 @ 12:50 PM
Study NCT ID: NCT03598907
Status: TERMINATED
Last Update Posted: 2020-07-02
First Post: 2018-06-30

Brief Title: Point-of-care Management of Coagulopathy in Lung Transplantation
Sponsor: University Hospital Motol
Organization: University Hospital Motol

Study Overview

Official Title: Point-of-care POC Approach to Management of Coagulopathy in Lung Transplantation Versus Standard Approach and Their Effect on Primary Graft Dysfunction PGD Randomized Controlled Study
Status: TERMINATED
Status Verified Date: 2020-06
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: After interim statistical analysis a statistician reccommended to stop study because results are significant and in favour of POC approach
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
Brief Summary: Pulmonary transplantation is a very demanding surgical procedure often accompanied by coagulopathy and severe perioperative bleeding The most common complication that develops within the first 72 hours after surgery is primary graft dysfunction PGD up to 30 in the most severe form The etiology of PGD is multifactorial One of the causes may be the amount of perioperative blood loss Intravascular volume is normally maintained by the administration of crystalloid and colloid solutions and fresh frozen plasma which is also used to treat coagulopathy however it is administered at the discretion of the anaesthetist and his experience practically meaning blindly In the field of the allogeneous ischemic organ these substitution solutions essentially become another allogeneous material and can cause undesired immunomodulation and contribute to the development of PGD In our prospective randomized trial 120 patients two patient groups will be investigated In the first group the coagulopathy and perioperative blood loss will be treated by the current standard approach by blind administration of fresh frozen plasma crystalloids and colloids In the second group the cause of coagulopathy will be diagnosed and treated according to the point-of-care POC results of ROTEM PFA 200 and Multiplate A colloidal solution of 5 albumin will be used to replace the circulating volume and maintain the oncotic pressure Investigators assume that the POC management of coagulopathy and bleeding in the second group will lead to a reduction in perioperative bleeding to reduced administration of infusion solutions and thus to a reduction of the incidence of PGD
Detailed Description: Introduction and project description

Primary graft dysfunction PGD in lung transplant patients is described as acute pulmonary damage occurring early in lung transplantation in the first 72 hours 1 2 sometimes referred to as ischemia - reperfusion injury 1 It is characterized by non-cardiac pulmonary edema and diffuse alveolar damage Clinically it is manifested by varying degrees of hypoxemia along with diffuse infiltrates in the X-ray of the lung There are more theories that try to explain the cause of PGD A number of factors such as cold organ ischemia mechanical irritation during organ reperfusion immunological inflammatory microbiological factors and many others associated with lung transplantation 2 3 may play a roll Depending on the severity of the clinical symptoms and the severity of X-ray findings according to International Society of Heart and Lung Transplantation ISHLT there are three types of PGD The incidence of PGD in its worst form Grade 3 in early post-transplantation period is being reported to be present in up to 30 and between 10-25 within 24-72 hours after organ reperfusion Lighter forms of PGD 1st and 2nd degree occur much more frequently 23 Lung affected by PGD is characteristically edematous and the gas exchange is significantly impaired due to damage to the endothelial barrier integrity of the vessels and the epithelial barrier of the lung tissue The presence of PGD significantly increases the morbidity and mortality of patients and significantly prolongs the time spent in invasive mechanical ventilation generally prolongs the time spent in intensive care unit and is a significant risk factor for development of chronic rejection of the transplanted lung 23

Lung transplantation is a demanding surgical procedure often associated with the development of coagulopathy and significant bleeding especially when extracorporeal membrane oxygenation ECMO is used perioperatively which is practically used in the most cases Blood loss is replaced by the administration of crystalloid and colloid solutions in order to maintain normovolemia and by administering FFP which is also used to treat coagulopathy despite the fact that the International Normalized Ratio INR of blood plasma is 15-16 These preparations are administered according to the anesthesiologists experience and practically blindly However their administration in patient significantly immunocompromised may mean a risk of immunomodulation and thus a deterioration of PGD In addition the administration of blood plasma is generally associated with higher morbidity and mortality of patients 1

On the other hand point-of-care POC monitoring of the hemocoagulation state using rotational thromboelastometry ROTEM and subsequent targeted coagulopathy therapy during the perioperative period and traumatic life threatening bleeding resulted in decreased bleeding intensity and consumption of transfusion products and this approach led to a reduction in morbidity and mortality of these patients 23

Also methods for evaluating primary haemostasis such as PFA 200 platelet function analyzer and aggregometry-Multiplate can be used as POC methods in the operating room especially for the diagnosis of coagulopathy accompanying the use of ECMO especially for the diagnosis of von Willebrands disease PFA 200 or for the diagnosis of thrombocytopathy Multiplate 1-4

All methods ROTEM PFA 200 and Multiplate are used to predict bleeding in cardiac surgery and hepatic transplantation and targeted therapy based on their results is associated with a reduction in blood transfusion FFP platelets erythrocytes administration reduced bleeding and reduced morbidity and mortality 5-7

Therefore it can reasonably be assumed that a similar positive benefit of this POC approach can be expected even in patients undergoing lung transplantation

In this prospective controlled randomized study of 120 lung transplant patients investigators want to compare the incidence of PGD between a group of patients treated by standard blind approach and a new POC approach Investigators assume that in a group where diagnosis and therapy of coagulopathy and bleeding will be managed based on the results of the ROTEM PFA 200 and Multiplate tests the clot strength will be increased and this will lead to reduced perioperative blood loss reduced administration of infusion solutions and FFP and this will subsequently lead to reduced incidence of PGD

Hypothesis

Point-of-care approach to diagnosis of perioperative coagulopathy with ROTEM PFA 200 and Multiplate and its subsequent aimed therapy will improve blood clot and thus will reduce blood loss fluid infusion blood transfusion and subsequently the incidence of PGD

Methodology

Patients undergoing bilateral lung transplantation 120 patients will be randomized into 2 groups using computerised generator of random numbers The study protocol will be registered in the Clinical Research Database and a clinical trial number CTN will be obtained and written informed consent will be obtained from patients before lung transplantation

The first group of existing standard care - the approach to bleeding patient will be based on clinical experience of the anaesthetist practically meaning administering crystalloids colloids hydroxyethyl starch or gelatin fresh frozen plasma and erythrocytes to restore normovolemia and platelets fibrinogen prothrombin complex concentrate von Willebrand factor tranexamic acid all products giving blindly when it comes to diagnosis and treatment of coagulopathy

The second group of point-of-care approach to the diagnosis and treatment of perioperative bleeding and coagulopathy will be conducted on the basis of the results of the POC methods ROTEM PFA 200 and Multiplate prothrombin complex concentrate fibrinogen platelets von Willebrand factor tranexamic acid A solution of 5 albumin and erythrocytes to keep haemoglobin level over 100 gl as it is critical for normal primary haemostasis will be used to keep normal circulating volume and to compensate for perioperative blood loss

Blood samples will obtained and analysed by ROTEM PFA 200 and Multiplate as well as the level and function of von Willebrand factor multimers assay ristocetin cofactor and collagen binding assay will be performed in all patients

1 before lung transplantation upon patient arrival to hospital before surgery as a control
2 after lung transplantation during admission of patient to postoperative intensive care unit
3 in the POC group also in the operating room ROTEM Multiplate and PFA 200 during surgery

The PGD score will be evaluated post-operatively and in the following way severity of PGD is defined in four degrees and is evaluated using partial arterial oxygen pressure PaO2 and inspired fraction of oxygen ratio FiO2 ratio and simultaneously evaluating X-ray finding of the lungs as soon as possible after reperfusion time 0 and after 48 and 72 hours after lung reperfusion

Grade 0 - PaO2FiO2 ratio of any value but no pulmonary edema on chest X-ray
Grade 1 - PaO2FiO2 300 and presence of pulmonary edema on chest X-ray
Grade 2 - PaO2FiO2 200 - 300 and and presence of pulmonary edema on chest X-ray
Grade 3 - PaO2FiO2 200 and presence of pulmonary edema on chest X-ray or patients in need of postoperative ECMO support or nitric oxide therapy

To exclude the possible thrombotic complication of any of these approaches each patient will be screened ultrasonographically for venous thrombosis 72 hours postoperatively vena poplitea vena femoralis vena jugularis and vena subclavia bilat and thrombotic complications will compared between groups

Also other parameters will be compared between groups

clot strength and whole coagulation profile before and after surgery using ROTEM PFA 200 and Multiplate and evaluation of the functional level of von Willebrand factor Correlation of coagulation profile with blood loss in the operating room and postoperative blood loss will be also assessed
amount of perioperative blood loss in the operating room at the end of surgery and 24 hours after surgery blood loss will measured as amount of blood in the suction container in operating room and as amount of blood in the chest drain in ICU postoperatively
number of transfusion products administered in operating room and in postoperative ICU
duration of invasive and noninvasive mechanical ventilation and time to extubation hours duration of stay in the postoperative ICU and overall in hospital before discharge home days
morbidity of patients SOFA score at 24 48 and 72 hours after lung transplantation morbidity and mortality among patients in 30 90 and 365 days
incidence of lung graft rejection during whole period of hospitalisation

Time schedule 4 years During the 3-years period recruitment of patients will be done and in the 4-th year data will be analysed and published in valuable journals

Investigators expect a lower consumption of blood transfusion products and infusion solutions in the POC group

In case of lower PGD incidence in the POC group investigators expect shorter time of mechanical ventilation a shorter period of hospitalization at the postoperative ICU and in the hospital overall and a lower incidence of pulmonary graft rejection

Investigators expect lower morbidity and mortality of patients in the POC group

Investigators also believe that the POC approach will reduce the total hospitalisation costs

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: False
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None