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Diuretic Versus Placebo in Pulmonary Embolism

Information source: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Pulmonary Embolism With Right Ventricle Enlargement

Intervention: Diuretics : Furosemide (Drug); Placebo (Drug)

Phase: Phase 3

Status: Not yet recruiting

Sponsored by: Assistance Publique - Hôpitaux de Paris

Official(s) and/or principal investigator(s):
Jean-Luc DUBOIS-RANDE, PU-PH, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris

Overall contact:
Jean-Luc DUBOIS-RANDE, PU-PH, Phone: (0)1 49 81 36 02, Ext: +33, Email: jean-luc.duboisrande@hmn.aphp.fr

Summary

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.

Clinical Details

Official title: Diuretic Versus Placebo in Pulmonary Embolism With Right Ventricular Enlargement: a Double-blind Randomized Controlled Study

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome:

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

- Composite criteria including death, need for catecholamine, cardiac arrest and mechanical ventilation during hospitalization and at 1 month from inclusion - NYHA score

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

- NT-proBNP or BNP decrease at 24hours - Creatinin and liver enzymes variations at 24hours

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Locations and Contacts

Jean-Luc DUBOIS-RANDE, PU-PH, Phone: (0)1 49 81 36 02, Ext: +33, Email: jean-luc.duboisrande@hmn.aphp.fr

Henri Mondor Hospital, Creteil 94010, France; Not yet recruiting
Jean-Luc DUBOIS-RANDE, PU-PH, Phone: (0)1 49 81 36 02, Ext: +33, Email: jean-luc.duboisrande@hmn.aphp.fr
Dalila SELMANE, CRA, Phone: (0)1 49 81 33 86, Ext: +33, Email: dalila.selmane@hmn.aphp.fr
Pascal LIM, PH, Principal Investigator
Additional Information

Related publications:

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.

Lee FA. Hemodynamics of the right ventricle in normal and disease states. Cardiol Clin. 1992 Feb;10(1):59-67. Review.

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.

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.

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.

Starting date: November 2014
Last updated: October 16, 2014

Page last updated: August 23, 2015

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