Ignite Creation Date:
2024-05-05 @ 4:46 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00302601
Status:
TERMINATED
Last Update Posted:
2016-04-18
First Post:
2006-03-13
Brief Title:
Study of Diagnosis and Pathophysiology of Pulmonary Embolism APE 1 Trial
Sponsor:
Odense University Hospital
Organization:
Odense University Hospital
Study Overview
Official Title:
The Acute Pulmonary Embolism 1 APE 1 Trial Prospective Investigation of Scintigraphic Diagnosis and Pathophysiology of Right Heart Strain
Status:
TERMINATED
Status Verified Date:
2016-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Logistics failure and staffscanner shortage
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to
investigate which method and criterion for diagnosing pulmonary embolism is the best and
determine the relationship between blood vessel constriction and clot size in patients developing heart failure
investigate which method and criterion for diagnosing pulmonary embolism is the best and
determine the relationship between blood vessel constriction and clot size in patients developing heart failure
Detailed Description:
INTRODUCTION This project assesses both scintigraphic diagnosis and the pathophysiology of right heart strain in acute pulmonary embolism The primary purposes are to validate various scintigraphic methods with pulmonary angiography as the standard of reference purpose A Furthermore this project examines the relative contributions of 1 vascular obstruction 2 vasoactive mediators and 3 co-morbidity to the generation of right heart strain purpose B
BACKGROUND FOR PURPOSE A Acute pulmonary embolism is a life threatening condition Early intervention can be lifesaving but treatment is associated with severe side effects Thus establishing accurate diagnosis is necessary Clinical presentation and physical examination have proven insufficient for this purpose This is also true for basic diagnostic investigations eg electrocardiography arterial blood gas analysis and chest x-ray which are considered standard tests in patients with symptoms consistent with cardiopulmonary disease
For several decades lung scintigraphy has been considered a cornerstone in the diagnosis of acute pulmonary embolism Planar two-dimensional images of the pulmonary perfusion are obtained using a gamma camera after intravenous injection of radiolabelled microparticles depicting perfusion defects caused by eg a pulmonary embolus Similarly ventilatory function can be assessed two-dimensionally by planar scintigraphic imaging following inhalation of a radioactive gas or aerosol Lung scintigraphy has certain limitations primarily related to image interpretation The PIOPED criteria based on the combined ventilation-perfusion scintigraphy have gained global acceptance but are often inconclusive and give rise to misunderstandings A different set of interpretation criteria provided by the PISA-PED study group are based solely on perfusion imaging Opposite the PIOPED criteria PISA-PED criteria are always conclusive and exhibits both high sensitivity and specificity The latter have however not gained the same widespread acceptance as the PIOPED criteria It remains uncertain which set of criteria is the better to confirm or exclude the diagnosis of acute pulmonary A prospective trial evaluating both PIOPED criteria original and revised and PISA-PED criteria against a valid standard of reference therefore seems appropriate
The more resource demanding single photon emission computed tomography SPECT has recently been subject to renewed interest in the diagnosis of acute pulmonary embolism but it remains unclear whether this technique offers additional information compared to conventional planar imaging SPECT offers three-dimensional images but otherwise the technique is similar to the methods described for planar images Combining the PISA-PED criteria and SPECT imaging has not yet been tested in a prospective trial but it seems highly relevant
Since the diagnosis is often suspected several times in the same patient the ability to distinguish acute and chronic changes in the scintigrams are essential It is however unclear to what extend and how fast the scintigraphic changes resolve This has great implications in scintigraphic control of patients recovering from acute pulmonary embolism
A trial regarding the statements above requires a reliable method to test whether the patient is suffering from acute pulmonary embolism or not a standard of reference Pulmonary angiography is traditionally conceived as the standard of reference in acute pulmonary embolism but only a few newer studies employ this technique
BACKGROUND FOR PURPOSE B Right heart strain is a common finding in acute pulmonary embolism It is a result of the sudden increase in pressure in the pulmonary circulation Ultrasonographic examination of the heart by echocardiography is suitable to demonstrate this condition and this finding in a patient with acute pulmonary embolism is associated with a considerably worse prognosis The degree of right heart strain is not exclusively determined by extension or size of the embolus There is substantial evidence of the influence of both co-morbidity and the release of vasoactive mediators on the extend of right heart strain The exact interplay between these three factors is not completely understood in humans Albeit this can have significant implications on therapy since pharmacological manipulation of vascular tone in the pulmonary circulation is possible This treatment is however not without risk and no well-designed study has yet addressed these issues in patients with acute pulmonary embolism Several case reports on successful treatment with vasodilation eg with inhaled nitric oxide have been published A more profound understanding of the etiology of acute right heart failure in acute pulmonary embolism is therefore desirable What is the individual contribution of 1 clot burden 2 release of vasoactive mediators and 3 co-morbidity
Recently acute pulmonary embolism has been divided into three categories depending on clinical presentation and echocardiographic findings 1 massive in which the patient suffers from cardiac arrest or cardiogenic shock Most authorities agree that these patients should be treated with fibrinolytic agents 2 Non-massive with no signs of shock or right heart strain In these patients there is no indication for fibrinolytic agents 3 Sub-massive with no manifestations of shock but echocardiographic findings consistent with right heart strain The indication for fibrinolytic treatment in this last group is unresolved This study will address whether simple methods eg peripheral blood sampling and perfusion scintigraphy can determine the primary mechanism in the generation of right heart strain in the individual patient
A later not yet planned intervention study based on the abovementioned knowledge could then address the following question Should the patient with sub-massive pulmonary embolism receive treatment with fibrinolytic agents in the case of major clot burden and minor degree of pulmonary vasoconstriction or vasodilators minor clot burden major degree of pulmonary vasoconstriction
BACKGROUND FOR PURPOSE A Acute pulmonary embolism is a life threatening condition Early intervention can be lifesaving but treatment is associated with severe side effects Thus establishing accurate diagnosis is necessary Clinical presentation and physical examination have proven insufficient for this purpose This is also true for basic diagnostic investigations eg electrocardiography arterial blood gas analysis and chest x-ray which are considered standard tests in patients with symptoms consistent with cardiopulmonary disease
For several decades lung scintigraphy has been considered a cornerstone in the diagnosis of acute pulmonary embolism Planar two-dimensional images of the pulmonary perfusion are obtained using a gamma camera after intravenous injection of radiolabelled microparticles depicting perfusion defects caused by eg a pulmonary embolus Similarly ventilatory function can be assessed two-dimensionally by planar scintigraphic imaging following inhalation of a radioactive gas or aerosol Lung scintigraphy has certain limitations primarily related to image interpretation The PIOPED criteria based on the combined ventilation-perfusion scintigraphy have gained global acceptance but are often inconclusive and give rise to misunderstandings A different set of interpretation criteria provided by the PISA-PED study group are based solely on perfusion imaging Opposite the PIOPED criteria PISA-PED criteria are always conclusive and exhibits both high sensitivity and specificity The latter have however not gained the same widespread acceptance as the PIOPED criteria It remains uncertain which set of criteria is the better to confirm or exclude the diagnosis of acute pulmonary A prospective trial evaluating both PIOPED criteria original and revised and PISA-PED criteria against a valid standard of reference therefore seems appropriate
The more resource demanding single photon emission computed tomography SPECT has recently been subject to renewed interest in the diagnosis of acute pulmonary embolism but it remains unclear whether this technique offers additional information compared to conventional planar imaging SPECT offers three-dimensional images but otherwise the technique is similar to the methods described for planar images Combining the PISA-PED criteria and SPECT imaging has not yet been tested in a prospective trial but it seems highly relevant
Since the diagnosis is often suspected several times in the same patient the ability to distinguish acute and chronic changes in the scintigrams are essential It is however unclear to what extend and how fast the scintigraphic changes resolve This has great implications in scintigraphic control of patients recovering from acute pulmonary embolism
A trial regarding the statements above requires a reliable method to test whether the patient is suffering from acute pulmonary embolism or not a standard of reference Pulmonary angiography is traditionally conceived as the standard of reference in acute pulmonary embolism but only a few newer studies employ this technique
BACKGROUND FOR PURPOSE B Right heart strain is a common finding in acute pulmonary embolism It is a result of the sudden increase in pressure in the pulmonary circulation Ultrasonographic examination of the heart by echocardiography is suitable to demonstrate this condition and this finding in a patient with acute pulmonary embolism is associated with a considerably worse prognosis The degree of right heart strain is not exclusively determined by extension or size of the embolus There is substantial evidence of the influence of both co-morbidity and the release of vasoactive mediators on the extend of right heart strain The exact interplay between these three factors is not completely understood in humans Albeit this can have significant implications on therapy since pharmacological manipulation of vascular tone in the pulmonary circulation is possible This treatment is however not without risk and no well-designed study has yet addressed these issues in patients with acute pulmonary embolism Several case reports on successful treatment with vasodilation eg with inhaled nitric oxide have been published A more profound understanding of the etiology of acute right heart failure in acute pulmonary embolism is therefore desirable What is the individual contribution of 1 clot burden 2 release of vasoactive mediators and 3 co-morbidity
Recently acute pulmonary embolism has been divided into three categories depending on clinical presentation and echocardiographic findings 1 massive in which the patient suffers from cardiac arrest or cardiogenic shock Most authorities agree that these patients should be treated with fibrinolytic agents 2 Non-massive with no signs of shock or right heart strain In these patients there is no indication for fibrinolytic agents 3 Sub-massive with no manifestations of shock but echocardiographic findings consistent with right heart strain The indication for fibrinolytic treatment in this last group is unresolved This study will address whether simple methods eg peripheral blood sampling and perfusion scintigraphy can determine the primary mechanism in the generation of right heart strain in the individual patient
A later not yet planned intervention study based on the abovementioned knowledge could then address the following question Should the patient with sub-massive pulmonary embolism receive treatment with fibrinolytic agents in the case of major clot burden and minor degree of pulmonary vasoconstriction or vasodilators minor clot burden major degree of pulmonary vasoconstriction
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None