title: Designing and conducting a cluster-randomized trial of ICU admission for the elderly patients: the ICE-CUB 2 study.
abstract: BACKGROUND
  The benefit of ICU admission for elderly patients remains controversial. This report highlights the methodology, the feasibility of and the ethical and logistical constraints in designing and conducting a cluster-randomized trial of intensive care unit (ICU) admission for critically ill elderly patients.
  
  
  METHODS
  We designed an interventional open-label cluster-randomized controlled trial in 24 centres in France. Clusters were healthcare centres with at least one emergency department (ED) and one ICU. Healthcare centres were randomly assigned either to recommend a systematic ICU admission (intervention group) or to follow standard practices regarding ICU admission (control group). Clusters were stratified by the number of ED annual visits (<44,616 or >44,616 visits), the presence or absence of a geriatric ward and the geographical area (Paris area vs other regions in France). All elderly patients (≥75 years of age) who got to the ED were assessed for eligibility. Patients were included if they had one of the pre-established critical conditions, a preserved functional status as assessed by an ADL scale ≥4 (0 = very dependent, 6 = independent), a preserved nutritional status (subjectively assessed by physicians) and without active cancer. Exclusion criteria were an ED stay >24 h, a secondary referral to the ED and refusal to participate. The primary outcome was the mortality at 6 months calculated at the individual patient level. Secondary outcomes were ICU and hospital mortality, as well as ADL scale and quality of life (as assessed by the SF-12 Health Survey) at 6 months.
  
  
  RESULTS
  Between January 2012 and April 2015, 3036 patients were included in the trial, 1518 patients in 11 clusters allocated to intervention group and 1518 patients in 13 clusters allocated to standard care. There were 51 protocol violations.
  
  
  CONCLUSIONS
  The ICE-CUB 2 trial was deemed feasible and ethically acceptable. The ICE-CUB 2 trial will be the first cluster-randomized trial to assess the benefits of ICU admission for selected elderly patients on long-term mortality. Trial registration Clinical trials.gov identifier: NCT01508819.
authors.affiliation: Hôpital Saint-Antoine, Service de Réanimation Médicale (Intensive Care Unit - ICU), Assistance Publique - Hôpitaux de Paris (AP-HP), 184 rue du Faubourg Saint-Antoine, 75012, Paris, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Boumendil
authors.affiliation: Hôpital Avicenne, Service d'Accueil des Urgences (SAU, Emergency Department), AP-HP, 93009, Bobigny, France.
authors.forename: Maguy
authors.initials: M
authors.lastname: Woimant
authors.affiliation: ICU, CHU de Dijon, 21079, Dijon, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Quenot
authors.affiliation: SAU, Hôpital Saint-Joseph, 75014, Paris, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Rooryck
authors.affiliation: SAU, CHU de Grenoble, 38700, Grenoble, France.
authors.forename: Foued
authors.initials: F
authors.lastname: Makhlouf
authors.affiliation: Hôpital Saint-Antoine, SAU, AP-HP, 75012, Paris, France.
authors.forename: Youri
authors.initials: Y
authors.lastname: Yordanov
authors.affiliation: Hôpital Pitié Salpétrière, SAU, AP-HP, 75013, Paris, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Delerme
authors.affiliation: Hôpital Cochin, SAU, AP-HP, 75014, Paris, France.
authors.forename: Khalil
authors.initials: K
authors.lastname: Takun
authors.affiliation: Hôpital Tenon, SAU, AP-HP, 75020, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ray
authors.affiliation: SAU, Hôpital Delafontaine, 93200, Saint Denis, France.
authors.forename: Marie-Clément
authors.initials: MC
authors.lastname: Kouka
authors.affiliation: SAU, Hôpital Robert Ballanger, 93602, Aulnay-Sous-Bois, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Poly
authors.affiliation: ICU, Hôpital Saint Joseph, 75014, Paris, France.
authors.forename: Maité
authors.initials: M
authors.lastname: Garrouste-Orgeas
authors.affiliation: Hôpital Saint-Antoine, Acute Geriatric Ward, AP-HP, 75012, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Hôpital Saint-Antoine, URC Est, AP-HP, 75012, Paris, France.
authors.forename: Tabasome
authors.initials: T
authors.lastname: Simon
authors.affiliation: Hôpital Ambroise Paré, URC Ouest, AP-HP, 92104, Boulogne-Billancourt, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Azerad
authors.affiliation: Department of Anesthesiology and Critical Care, Université Laval, Québec, QC, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Leblanc
authors.affiliation: Hôpital Saint-Antoine, SAU, AP-HP, 75012, Paris, France.|UPMC Univ Paris 06, Sorbonne Universités, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Pateron
authors.affiliation: Hôpital Saint-Antoine, Service de Réanimation Médicale (Intensive Care Unit - ICU), Assistance Publique - Hôpitaux de Paris (AP-HP), 184 rue du Faubourg Saint-Antoine, 75012, Paris, France. bertrand.guidet@aphp.fr.|UPMC Univ Paris 06, Sorbonne Universités, Paris, France. bertrand.guidet@aphp.fr.|UMR_S 1136, Institut Pierre Louis d'Épidémiologie et de Santé Publique, INSERM, 75013, Paris, France. bertrand.guidet@aphp.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Guidet
keywords: Elderly; Ethics; Intensive care