Diuretic Versus Placebo in Pulmonary Embolism (DiPER)

October 18, 2017 updated by: Assistance Publique - Hôpitaux de Paris

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

270

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Placebo in one single direct intra venous injection
Active Comparator: Diuretics
Drug: Diuretics : Furosemide
Furosemide 80mg in one single direct intra venous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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.
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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.
48 hours
- Composite criteria including death, need for catecholamine, cardiac arrest and mechanical ventilation during hospitalization and at 1 month from inclusion - NYHA score
Time Frame: In hospital and 1 month
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
Time Frame: 24 hours abd 1 month
RV/LV ratio (diameters and surfaces)
24 hours abd 1 month
- NT-proBNP or BNP decrease at 24hours - Creatinin and liver enzymes variations at 24hours
Time Frame: 24 hours
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Jean-Luc DUBOIS-RANDE, PU-PH, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 13, 2015

Primary Completion (Anticipated)

April 1, 2018

Study Completion (Anticipated)

May 1, 2018

Study Registration Dates

First Submitted

October 16, 2014

First Submitted That Met QC Criteria

October 16, 2014

First Posted (Estimate)

October 20, 2014

Study Record Updates

Last Update Posted (Actual)

October 19, 2017

Last Update Submitted That Met QC Criteria

October 18, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AOM 130519

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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