title: 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.
abstract: BACKGROUND
  In acute pulmonary embolism (PE), poor outcome is usually related to right ventricular (RV) failure due to the increase in RV afterload. Treatment of PE with RV failure without shock is controversial and usually relies on fluid expansion to increase RV preload. However, several studies suggest that fluid expansion may worsen acute RV failure by increasing RV dilation and ischaemia, and increase left ventricular compression by RV dilation. By reducing RV enlargement, diuretic treatment may break this vicious circle and provide early improvement in normotensive patients referred for acute PE with RV failure.
  
  
  METHODS
  The Diuretic versus placebo in Pulmonary Embolism with Right ventricular enlargement trial (DiPER) is a prospective, multicentre, randomised (1:1), double-blind, placebo controlled study assessing the superiority of furosemide as compared with placebo in normotensive patients with confirmed acute PE and RV dilation (diagnosed on echocardiography or CT of the chest) and positive brain natriuretic peptide result. The primary end point will be a combined clinical criterion derived from simplified Pulmonary Embolism Severity Index (PESI) score and evaluated at 24 h. It will include: (1) urine output >0.5 mL/kg/min for the past 24 h; (2) heart rate <110 bpm; (3) systolic blood pressure >100 mm Hg and (4) arterial oxyhaemoglobin level >90%. Thirty-day major cardiac events defined as death, cardiac arrest, mechanical ventilation, need for catecholamine and thrombolysis, will be evaluated as a secondary end point. Assuming an increase of 30% in the primary end point with furosemide and a β risk of 10%, 270 patients will be required.
  
  
  BACKGROUND
  Ethical approval was received from the ethical committee of Ile de France (2014-001090-14). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations.
  
  
  BACKGROUND
  NCT02268903.
authors.affiliation: Department of Cardiology, Hopital Henri Mondor, Creteil, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Gallet
authors.affiliation: Division of Respiratory and Intensive Care, Hopital Europeen Georges Pompidou, Paris, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Meyer
authors.affiliation: Department of Cardiology, Hopital Henri Mondor, Creteil, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Ternacle
authors.affiliation: Department of Cardiology, CHU Rangueil, Toulouse, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Biendel
authors.affiliation: Department of Cardiology and Cardiac Imaging, CHU, Tours, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Brunet
authors.affiliation: Department of Cardiology, CHRU, Besancon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Meneveau
authors.affiliation: Department of Cardiology, Hopital Saint-Joseph, Marseille, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Rosario
authors.affiliation: Respiratory Department, CHRU de la Cavale Blanche, Brest, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Couturaud
authors.affiliation: Emergency Department, CHRU Lapeyronie, Montpellier, France.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Sebbane
authors.affiliation: Department of Cardiology, CHRU, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lamblin
authors.affiliation: Department of Cardiology, CHU, Grenoble, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Bouvaist
authors.affiliation: Department of Cardiology, CHU, Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Coste
authors.affiliation: Department of Pneumology, Hopital Henri Mondor, Creteil, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Maitre
authors.affiliation: Clinical Research Department, Hopital Henri Mondor, Creteil, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bastuji-Garin
authors.affiliation: Department of Cardiology, Hopital Henri Mondor, Creteil, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Dubois-Rande
authors.affiliation: Department of Cardiology, Hopital Henri Mondor, Creteil, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lim
mesh_terms: D000328:Adult; D001794:Blood Pressure; D002985:Clinical Protocols; D004232:Diuretics / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005602:France; D005665:Furosemide / Q000494:pharmacology / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D010919:Placebos; D011655:Pulmonary Embolism / Q000150:complications / Q000188:drug therapy*; D012107:Research Design; D012720:Severity of Illness Index; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy* / Q000209:etiology
chemical_list: D004232:Diuretics; D010919:Placebos; D005665:Furosemide