Pulmonary Embolism With Right Ventricle Enlargement Clinical Trial
— DiPEROfficial title:
Diuretic Versus Placebo in Pulmonary Embolism With Right Ventricular Enlargement: a Double-blind Randomized Controlled Study
Pulmonary Embolism (PE) is a frequent and severe disease with an annual incidence of about
75000 cases in France and a short-term mortality rate of about 10%. Death is usually related
to an acute right ventricular (RV) failure due to the increase in right ventricular
afterload. Treatment of PE with RV failure consists in fluid expansion and thrombolysis in
case of shock. However several studies suggest that fluid expansion may worsen acute RV
failure by increasing RV dilatation and ischemia and left ventricular compression by RV
dilatation. Thus, current guidelines regarding PE treatment remain unclear about the use of
fluid expansion. In a preliminary study published by our group, we showed that diuretic
treatment in the setting of PE with RV dilatation is safe and is associated with an increase
in urine output, a decrease in heart rate and an increase in SpO2 in normotensive patients
with oliguria. This may be related to the decrease of ventricular interdependence and
enhancement of both LV and RV function.
The main objective of the study is to evaluate the 24-hours clinical benefit of furosemide in
patients referred for acute PE with RV dilatation compared to placebo. The combination of
urine output and sPESI clinical parameters reflects hemodynamic status. It is relevant as it
indicates the disappearance of pre-shock symptoms and is therefore associated with a lower
event risk. Thus, it allows early discharge of the patients from the intensive care unit.
| Status | Recruiting |
| Enrollment | 270 |
| Est. completion date | May 2018 |
| Est. primary completion date | April 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: Patients aged 18 years and over with 1. Symptomatic acute pulmonary embolism with first clinical symptoms within 15 days, and objectively confirmed by CT scan 2. RV dysfunction (=1 criterion) confirmed by elevated BNP value or echocardiography or spiral computed tomography of the chest: - Echocardiography o Right/Left ventricular end diastolic diameter > 1(apical or subcostal 4-chamber view) - Computed tomography o Right/Left short-axis diameter ratio>0.9 (transverse plane) - Positive Nt-proBNP (>600) or BNP>200 pg/mL 3. One abnormal following PESI criteria - Heart Rate>110/min - Systolic blood pressure<100mmHg - Arterial oxyhemoglobin level<90% on room air or after 5 minutes of oxygen withdrawal. Exclusion Criteria: - Cardiogenic shock requiring thrombolysis - Previous significant left ventricular insufficiency (LVEF<45%) - Systolic blood pressure<90mmHg at admission - Age = 18 years - Pregnancy - No health insurance - Patients deprived of liberty or under legal protection - Creatinin clearance <30mL/min/m² - hypersensibility to furosemide or its excipients - functional renal insufficiency - Hepatic encephalopathy - Urinary tracks obstruction - Hypovolemia or dehydration. - Sever hypokalemia (K+ < 3mmol/L) - Severe hyponatremia (Na+ < 125mmol/L) - Ongoing hepatitis and hepatic insufficiency severe in patients with renal insufficiency or dialysis |
| Country | Name | City | State |
|---|---|---|---|
| France | Henri Mondor Hospital | Creteil |
| Lead Sponsor | Collaborator |
|---|---|
| Assistance Publique - Hôpitaux de Paris |
France,
Goldhaber SZ, Haire WD, Feldstein ML, Miller M, Toltzis R, Smith JL, Taveira da Silva AM, Come PC, Lee RT, Parker JA, et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet. 1993 Feb 27;341(8844):507-11. — View Citation
Lee FA. Hemodynamics of the right ventricle in normal and disease states. Cardiol Clin. 1992 Feb;10(1):59-67. Review. — View Citation
Perlroth DJ, Sanders GD, Gould MK. Effectiveness and cost-effectiveness of thrombolysis in submassive pulmonary embolism. Arch Intern Med. 2007 Jan 8;167(1):74-80. — View Citation
Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP; ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008 Sep;29(18):2276-315. doi: 10.1093/eurheartj/ehn310. Epub 2008 Aug 30. — View Citation
Wood KE. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest. 2002 Mar;121(3):877-905. Review. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Primary end point will be a combined clinical criterion, to reach the primary endpoint, patients have to meet all the following criteria: - Urine output> 0.5ml/kg/h - Normalization of clinical parameters of simplified PESI score | Normalization of clinical parameters of simplified PESI score : Heart Rate<110/min Systolic blood pressure=100mmHg Arterial oxyhemoglobin level>90% on room air or after 5 minutes of oxygen withdrawal. |
24 hours | |
| Secondary | patients have to meet all the four following criteria: - Urine output> 0.5ml/kg/h over 24 hours - Normalization of clinical parameters of simplified PESI score - Urine output | Normalization of clinical parameters of simplified PESI score : Heart Rate<110/min Systolic blood pressure=100mmHg Arterial oxyhemoglobin level>90% on room air or after 5 minutes of oxygen withdrawal. |
48 hours | |
| Secondary | - Composite criteria including death, need for catecholamine, cardiac arrest and mechanical ventilation during hospitalization and at 1 month from inclusion - NYHA score | In hospital and 1 month | ||
| Secondary | o RV/LV ratio and decrease from baseline o Systolic pulmonary pressure and decrease from baseline o Tricuspid annular plane systolic expansion (TAPSE) at o Tricuspid annular plane systolic expansion (TAPSE) variation from baseline | RV/LV ratio (diameters and surfaces) | 24 hours abd 1 month | |
| Secondary | - NT-proBNP or BNP decrease at 24hours - Creatinin and liver enzymes variations at 24hours | 24 hours |