Low Dose of Hydrocortisone and Fludrocortisone in Adult Cardiogenic Shock. (COCCA)

Low Dose of Hydrocortisone and Fludrocortisone in Adult Cardiogenic Shock. A Multicenter, Prospective, Double-blind, Randomized, Placebo-controlled Study

The purpose of this randomized controlled trial is to evaluate the hemodynamic effect of low dose corticosteroid therapy (hydrocortisone and fludrocortisone) in the treatment of adult cardiogenic shock.

Study Overview

• Status: Completed
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Other: Placebo; Combination product: Hydrocortisone + Flucortac

Detailed Description

Cardiogenic shock is a serious condition with a high mortality rate, characterized by acute dysfunction of the heart pump. Critical illness-related corticosteroid insufficiency is a pathophysiological concept, first described in septic shock. It is characterized by an impairment of the hypothalamic pituitary axis during critical illness. Its diagnosis is usually suggested by an inappropriate response to the adrenal stimulation test. The results of corticosteroid supplementation studies in septic shock are controversial, but most of these studies demonstrate that corticosteroid therapy improves reversal of shock.

The concept of critical illness-related corticosteroid insufficiency has recently been expanded to cardiogenic shock. The latter has many physiopathological similarities with septic shock. However, no studies have evaluated the effect of supplemental corticosteroid supplementation in cardiogenic shock.

The purpose of this study is to evaluate the hemodynamic effect of low dose corticosteroid therapy in the treatment of adult cardiogenic shock.

This study is a multicenter, randomized, double blinded, placebo controlled trial comparing intravenous hydrocortisone (50 mg intravenously every 6 hours) plus enteral fludrocortisone (50 µg/day) with placebo for seven days in critically ill patients with cardiogenic shock.

The primary endpoint for this trial will be catecholamine-fee days at day-7. Secondary endpoints will include all-cause mortality at 28 and 90 days after randomisation.

Several pre-defined sub-groups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use...

380 patients will be enrolled in this study at approximately 20 study sites. Each patient will be followed-up for 90 days.

• Study Type: Interventional
• Enrollment (Actual): 380
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Armand MEKONTSO DESSAP, MD; Phone Number: (+33)1 46 25 24 33; Email: armand.dessap@aphp.fr
• Study Contact Backup: Name: François BAGATE,, MD; Phone Number: (+33)1 49 81 23 89; Email: francois.bagate@aphp.fr

Study Locations

• France
  • Boulogne-Billancourt, France, 92100
    • Hôpital Ambroise Paré
  • Jossigny, France, 77600
    • CH de Marne la Vallée - Site Jossigny
  • Lille, France, 59000
    • CHU Lille - Institut Coeur Poumon
  • Lyon, France, 69007
    • Centre Hospitalier Saint Joseph Saint Luc
  • Massy, France, 91300
    • Hôpital Privé Jacques Cartier
  • Montpellier, France, 34090
    • Hôpital Arnaud-de-Villeneuve
  • Neuilly sur seine, France, 92200
    • CMC Ambroise Paré
  • Nîmes, France, 30029
    • CHU de Nîmes
  • Paris, France, 75014
    • Groupe Hospitalier Paris Saint Joseph
  • Paris, France, 75015
    • Hopital Europeen Georges-Pompidou
  • Paris, France, 75014
    • Hôpital COCHIN
  • Paris, France, 75018
    • Hôpital Bichat
  • Paris, France, 75013
    • Hôpitaux Universitaires Pitié Salpêtrière
  • Pontoise, France, 95300
    • CH Pontoise
  • Saint-Denis, France, 93200
    • Centre cardiologique du nord saint denis
  • Strasbourg, France, 67000
    • CHU de Strasbourg
  • Toulouse, France, 31400
    • Hopital Rangueil
  • Tours, France, 37000
    • CHRU Hôpitaux De Tours
  • Ile De France
    • Paris, Ile De France, France
      • Hopital Henri Mondor
  • Le Chasnay
    • Le Chesnay, Le Chasnay, France, 78150
      • Hôpital Parly II
  • Villeneuve Saint Georges
    • Villeneuve-Saint-Georges, Villeneuve Saint Georges, France, 94190
      • CH Intercommunal de Villeneuve Saint Georges

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged ≥18 years

2. Cardiogenic shock state, according to the consensual definition:

   1. Systemic arterial hypertension (systolic blood pressure <90 mmHg or mean arterial pressure ≤ 65 mmHg) or signs of peripheral hypoperfusion, requiring treatment with catecholamines to maintain systolic blood pressure ≥ 90 mmHg and regression of signs of hypoperfusion;
   2. Presence of at least one sign of systemic hypoperfusion among the following: marbling, oliguria ≤ 25 ml / h, impairment of consciousness, arterial hyperlactatemia> 2 mmol / L;
   3. Presence of at least one sign of hypocontractility or low flow among the following: cardiac index ≤ 2.2 L / min / m2, left ventricular ejection fraction (LVEF) ≤ 40% or full time velocity (ITV) under aortic ≤ 18 cm, or need for catecholamines to maintain an index
   4. Clinical signs of left and / or right cardiac congestion (clinical sign of acute cardiogenic pulmonary edema or jugular turgor or edema of the lower limbs), radiological (bilateral alveolar opacities compatible with acute cardiogenic pulmonary edema), echocardiography (elevation of filling pressures of the left ventricle measured with Doppler: E / A> 2 if LVEF ≤40% or E / Ea> 13 if LVEF> 40%; or estimated PAPS> 35mmHg) or with right cardiac catheterization (pulmonary artery occlusion pressures> 15mmHg or PAPm> 25mmHg)
3. Having received informed information about the study and having signed a consent to participate in the study
4. Benefiting from a social security

Exclusion Criteria:

1. Cardiogenic shock state with catecholamine infusion for more than 24 hours;
2. Presence Presence of septic shock at inclusion;
3. Cardiopulmonary arrest recovered in the 7 days preceding inclusion with at least one early sign of poor prognosis among the following: no control, non-shockable rhythm, CAHP score (Cardiac Arrest Hospital Prognosis)> 150;
4. Patients already on circulatory support (ECMO) before inclusion (patients who are assisted after inclusion will not be excluded);
5. Cardiogenic shock on viral myocarditis;
6. Prior corticosteroid therapy (≥ 30 mg prednisone or equivalent ≥ 1 month);
7. Receiving one of the following treatments: ketoconazole, rifampicin, phenytoin, phenobarbital, cyclosporine and clarithromycin;
8. Known history of hypersensitivity to fludrocortisone or hydrocortisone;
9. Known pregnancy or breastfeeding;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo of hydrocortisone and placebo of fludrocortisone; Placebo of hydrocortisone as an iv bolus every 6 hours for seven days plus placebo of enteral fludrocortisone given once a day for seven days	Other: Placebo; Placebo
Experimental: Combination of hydrocortisone + fludrocortisone; Hydrocortisone will be given as 50 mg iv bolus every 6 hours for seven days and a tablet of 50 µg of fludrocortisone will be given once a day enterally for seven days	Combination product: Hydrocortisone + Flucortac; Low dose steroids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Patients not treated with corticosteroids at day 7	7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality at 28 and 90 days after randomisation	28 and 90 days after randomisation
Modification of the cardiac index	7 days
Length of stay in intensive care and hospital	28 and 90 days after randomisation
Duration of support by catecholamines	28 days after randomisation
Clearance of lactatemia	7 days
Number of patients use of mechanical ventilation	28 days after randomisation
Number of patients with Circulatory assistance	28 days after randomisation
Number of patients alive at day 7 without failure (SOFA) score)	7 days
Rate of patients with nosocomial infection	28 days after randomisation
Rates of patients requiring the introduction of intravenous insulin therapy after randomization	7 days
Modification of mean arterial pressure	7 days

Collaborators and Investigators

• Sponsor: CMC Ambroise Paré

Publications and helpful links

General Publications

• Mekontso Dessap A, Bagate F, Delmas C, Morichau-Beauchant T, Cholley B, Cariou A, Lattuca B, Moussa M, Mongardon N, Fard D, Schmidt M, Bougle A, Kerneis M, Vivier E, Roubille F, Duprey M, Decalf V, Genet T, Merzoug M, Audureau E, Squara P. Low-dose corticosteroid therapy for cardiogenic shock in adults (COCCA): study protocol for a randomized controlled trial. Trials. 2022 Jan 3;23(1):4. doi: 10.1186/s13063-021-05947-6.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2019
• Primary Completion (Actual): April 5, 2023
• Study Completion (Actual): April 5, 2023

Study Registration Dates

• First Submitted: November 21, 2018
• First Submitted That Met QC Criteria: December 11, 2018
• First Posted (Actual): December 12, 2018

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Mortality; Hydrocortisone; Steroids; Cardiogenic Shock; Adrenal insufficiency; Reversal of shock; Fludrocortisone
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Shock; Shock, Cardiogenic; Anti-Inflammatory Agents; Hydrocortisone
• Other Study ID Numbers: 2018/05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No