Diuretic Versus Placebo in Pulmonary Embolism

Phase 3

• Conditions: Pulmonary Embolism With Right Ventricle Enlargement
• Interventions: Drug: Placebo

• Registration Number: NCT02268903
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-10-16
• Study First Submitted QC: 2014-10-16
• Study First Posted: 2014-10-20
• Study Start: 2015-04-13
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-18
• Last Update Posted: 2017-10-19
• Primary Completion: 2018-04
• Study Completion: 2018-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 270

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
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	24 hours	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.

Secondary Outcome Measures

Name	Time	Method
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	48 hours	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.
- 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
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	24 hours abd 1 month	RV/LV ratio (diameters and surfaces)
- NT-proBNP or BNP decrease at 24hours - Creatinin and liver enzymes variations at 24hours	24 hours

Trial Locations

Locations (1)

Henri Mondor Hospital; 🇫🇷 Creteil, France