NCT02268903

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
270

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Apr 2015

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 16, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 20, 2014

Completed
6 months until next milestone

Study Start

First participant enrolled

April 13, 2015

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2018

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2018

Completed
Last Updated

October 19, 2017

Status Verified

October 1, 2017

Enrollment Period

3 years

First QC Date

October 16, 2014

Last Update Submit

October 18, 2017

Conditions

Pulmonary Embolism With Right Ventricle Enlargement

Keywords

Pulmonary EmbolismRight Ventricle failureDiuretics

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • 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

  • - 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

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

    24 hours

Study Arms (2)

Diuretics

ACTIVE COMPARATOR
Drug: Diuretics : Furosemide

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

Diuretics : FurosemideDRUG

Furosemide 80mg in one single direct intra venous injection

Diuretics
PlaceboDRUG

Placebo in one single direct intra venous injection

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients aged 18 years and over with
  • Symptomatic acute pulmonary embolism with first clinical symptoms within 15 days, and objectively confirmed by CT scan
  • 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
  • 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.

You may not qualify if:

  • 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)
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Henri Mondor Hospital

Créteil, 94010, France

RECRUITING

Related Publications (7)

  • 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. doi: 10.1378/chest.121.3.877.

    PMID: 11888976BACKGROUND

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

    PMID: 1739960BACKGROUND

  • Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie 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.

    PMID: 18757870BACKGROUND

  • 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. doi: 10.1001/archinte.167.1.74.

    PMID: 17210881BACKGROUND

  • 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. doi: 10.1016/0140-6736(93)90274-k.

    PMID: 8094768BACKGROUND

  • Lim P, Delmas C, Sanchez O, Meneveau N, Rosario R, Bouvaist H, Bernard A, Mansourati J, Couturaud F, Sebbane M, Coste P, Rohel G, Tardy B, Biendel C, Lairez O, Ivanes F, Gallet R, Dubois-Rande JL, Fard D, Chatelier G, Simon T, Paul M, Natella PA, Layese R, Bastuji-Garin S. Diuretic vs. placebo in intermediate-risk acute pulmonary embolism: a randomized clinical trial. Eur Heart J Acute Cardiovasc Care. 2022 Jan 12;11(1):2-9. doi: 10.1093/ehjacc/zuab082.

    PMID: 34632490DERIVED

  • Gallet R, Meyer G, Ternacle J, Biendel C, Brunet A, Meneveau N, Rosario R, Couturaud F, Sebbane M, Lamblin N, Bouvaist H, Coste P, Maitre B, Bastuji-Garin S, Dubois-Rande JL, Lim P. Diuretic versus placebo in normotensive acute pulmonary embolism with right ventricular enlargement and injury: a double-blind randomised placebo controlled study. Protocol of the DiPER study. BMJ Open. 2015 May 22;5(5):e007466. doi: 10.1136/bmjopen-2014-007466.

    PMID: 26002690DERIVED

MeSH Terms

Conditions

Pulmonary Embolism

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesEmbolismEmbolism and ThrombosisVascular DiseasesCardiovascular Diseases

Study Officials

  • Jean-Luc DUBOIS-RANDE, PU-PH

    Assistance Publique - Hôpitaux de Paris

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean-Luc DUBOIS-RANDE, PU-PH

CONTACT

(0)1 49 81 36 02jean-luc.duboisrande@hmn.aphp.fr

Romain GALLET, CCA

CONTACT

(0)1 49 81 36 02romain.gallet@yahoo.fr

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 16, 2014

First Posted

October 20, 2014

Study Start

April 13, 2015

Primary Completion

April 1, 2018

Study Completion

May 1, 2018

Last Updated

October 19, 2017

Record last verified: 2017-10

Locations

FR(1)