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

Primary Purpose

Cardiogenic Shock

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Hydrocortisone + Flucortac
Placebo
Sponsored by
CMC Ambroise Paré
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiogenic Shock focused on measuring Cardiogenic Shock, Steroids, Hydrocortisone, Fludrocortisone, Reversal of shock, Mortality, Adrenal insufficiency

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • Hôpital Henri MondorRecruiting
  • Hôpital Parly II
  • CH Intercommunal de Villeneuve Saint Georges
  • Hôpital Ambroise Paré
  • CH de Marne la Vallée - Site JossignyRecruiting
  • CHU Lille - Institut Cœur PoumonRecruiting
  • Centre Hospitalier Saint Joseph Saint LucRecruiting
  • Hôpital Privé Jacques Cartier
  • Hôpital Arnaud-de-VilleneuveRecruiting
  • CMC Ambroise ParéRecruiting
  • CHU de NîmesRecruiting
  • Hôpitaux Universitaires Pitié SalpêtrièreRecruiting
  • Groupe Hospitalier Paris Saint Joseph
  • Hôpital CochinRecruiting
  • Hôpital européen Georges-PompidouRecruiting
  • Hôpital Bichat
  • CH PontoiseRecruiting
  • Centre cardiologique du nord saint denisRecruiting
  • CHU de Strasbourg
  • Hopital RangueilRecruiting
  • CHRU Hôpitaux de ToursRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo of hydrocortisone and placebo of fludrocortisone

Combination of hydrocortisone + fludrocortisone

Arm Description

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

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

Outcomes

Primary Outcome Measures

Patients not treated with corticosteroids at day 7

Secondary Outcome Measures

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

Full Information

First Posted
November 21, 2018
Last Updated
June 13, 2022
Sponsor
CMC Ambroise Paré
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1. Study Identification

Unique Protocol Identification Number
NCT03773822
Brief Title
Low Dose of Hydrocortisone and Fludrocortisone in Adult Cardiogenic Shock.
Acronym
COCCA
Official Title
Low Dose of Hydrocortisone and Fludrocortisone in Adult Cardiogenic Shock. A Multicenter, Prospective, Double-blind, Randomized, Placebo-controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 19, 2019 (Actual)
Primary Completion Date
April 20, 2023 (Anticipated)
Study Completion Date
August 20, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CMC Ambroise Paré

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiogenic Shock
Keywords
Cardiogenic Shock, Steroids, Hydrocortisone, Fludrocortisone, Reversal of shock, Mortality, Adrenal insufficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
380 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo of hydrocortisone and placebo of fludrocortisone
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
Combination of hydrocortisone + fludrocortisone
Arm Type
Experimental
Arm Description
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
Intervention Type
Combination Product
Intervention Name(s)
Hydrocortisone + Flucortac
Intervention Description
Low dose steroids
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Patients not treated with corticosteroids at day 7
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Mortality at 28 and 90 days after randomisation
Time Frame
28 and 90 days after randomisation
Title
Modification of the cardiac index
Time Frame
7 days
Title
Length of stay in intensive care and hospital
Time Frame
28 and 90 days after randomisation
Title
Duration of support by catecholamines
Time Frame
28 days after randomisation
Title
Clearance of lactatemia
Time Frame
7 days
Title
Number of patients use of mechanical ventilation
Time Frame
28 days after randomisation
Title
Number of patients with Circulatory assistance
Time Frame
28 days after randomisation
Title
Number of patients alive at day 7 without failure (SOFA) score)
Time Frame
7 days
Title
Rate of patients with nosocomial infection
Time Frame
28 days after randomisation
Title
Rates of patients requiring the introduction of intravenous insulin therapy after randomization
Time Frame
7 days
Title
Modification of mean arterial pressure
Time Frame
7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged ≥18 years Cardiogenic shock state, according to the consensual definition: 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; 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; 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 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) Having received informed information about the study and having signed a consent to participate in the study Benefiting from a social security Exclusion Criteria: Cardiogenic shock state with catecholamine infusion for more than 24 hours; Presence Presence of septic shock at inclusion; 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; Patients already on circulatory support (ECMO) before inclusion (patients who are assisted after inclusion will not be excluded); Cardiogenic shock on viral myocarditis; Prior corticosteroid therapy (≥ 30 mg prednisone or equivalent ≥ 1 month); Receiving one of the following treatments: ketoconazole, rifampicin, phenytoin, phenobarbital, cyclosporine and clarithromycin; Known history of hypersensitivity to fludrocortisone or hydrocortisone; Known pregnancy or breastfeeding;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Armand MEKONTSO DESSAP, MD
Phone
(+33)1 46 25 24 33
Email
armand.dessap@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
François BAGATE,, MD
Phone
(+33)1 49 81 23 89
Email
francois.bagate@aphp.fr
Facility Information:
Facility Name
Hôpital Henri Mondor
City
Paris
State/Province
Ile De France
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Armand MEKONTSO DESSAP, MD
First Name & Middle Initial & Last Name & Degree
Armand MEKONTSO DESSAP, MD
First Name & Middle Initial & Last Name & Degree
François BAGATE, MD
Facility Name
Hôpital Parly II
City
Le Chesnay
State/Province
Le Chasnay
ZIP/Postal Code
78150
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CH Intercommunal de Villeneuve Saint Georges
City
Villeneuve-Saint-Georges
State/Province
Villeneuve Saint Georges
ZIP/Postal Code
94190
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Hôpital Ambroise Paré
City
Boulogne-Billancourt
ZIP/Postal Code
92100
Country
France
Individual Site Status
Not yet recruiting
Facility Name
CH de Marne la Vallée - Site Jossigny
City
Jossigny
ZIP/Postal Code
77600
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Lille - Institut Cœur Poumon
City
Lille
ZIP/Postal Code
59000
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Saint Joseph Saint Luc
City
Lyon
ZIP/Postal Code
69007
Country
France
Individual Site Status
Recruiting
Facility Name
Hôpital Privé Jacques Cartier
City
Massy
ZIP/Postal Code
91300
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Hôpital Arnaud-de-Villeneuve
City
Montpellier
ZIP/Postal Code
34090
Country
France
Individual Site Status
Recruiting
Facility Name
CMC Ambroise Paré
City
Neuilly sur seine
ZIP/Postal Code
92200
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre SQUARA, MD
Phone
0146415079
Email
recherche@clinique-a-pare.fr
First Name & Middle Initial & Last Name & Degree
Messaouda MERZOUG, PhD
Email
recherche@clinique-a-pare.fr
First Name & Middle Initial & Last Name & Degree
Pierre SQUARA, MD
First Name & Middle Initial & Last Name & Degree
Philippe ESTAGNASIE, MD
First Name & Middle Initial & Last Name & Degree
Alain BRUSSET, MD
First Name & Middle Initial & Last Name & Degree
Driss LAGHLEM, MD
Facility Name
CHU de Nîmes
City
Nîmes
ZIP/Postal Code
30029
Country
France
Individual Site Status
Recruiting
Facility Name
Hôpitaux Universitaires Pitié Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Name
Groupe Hospitalier Paris Saint Joseph
City
Paris
ZIP/Postal Code
75014
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Hôpital Cochin
City
Paris
ZIP/Postal Code
75014
Country
France
Individual Site Status
Recruiting
Facility Name
Hôpital européen Georges-Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Name
Hôpital Bichat
City
Paris
ZIP/Postal Code
75018
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CH Pontoise
City
Pontoise
ZIP/Postal Code
95300
Country
France
Individual Site Status
Recruiting
Facility Name
Centre cardiologique du nord saint denis
City
Saint-Denis
ZIP/Postal Code
93200
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tristan MORICHAU-BEAUCHANT, MD
Facility Name
CHU de Strasbourg
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Individual Site Status
Suspended
Facility Name
Hopital Rangueil
City
Toulouse
ZIP/Postal Code
31400
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clément DELMAS, MD
Facility Name
CHRU Hôpitaux de Tours
City
Tours
ZIP/Postal Code
37000
Country
France
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34980224
Citation
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.
Results Reference
derived

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Low Dose of Hydrocortisone and Fludrocortisone in Adult Cardiogenic Shock.

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