Low Dose of Hydrocortisone and Fludrocortisone in Adult Cardiogenic Shock.

Cardiogenic Shock Clinical Trial

— COCCA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03773822
• Other study ID #: 2018/05
• Status: Completed
• Phase: Phase 3
• Start date: April 19, 2019
• Est. completion date: April 5, 2023

Study information

• Verified date: November 2023
• Source: CMC Ambroise Paré
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 380
• Est. completion date: April 5, 2023
• Est. primary completion date: April 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Cardiogenic Shock
• Shock
• Shock, Cardiogenic

Intervention

Combination Product:
• Hydrocortisone + Flucortac
Low dose steroids

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
France	Hôpital Ambroise Paré	Boulogne-Billancourt
France	CH de Marne la Vallée - Site Jossigny	Jossigny
France	Hôpital Parly II	Le Chesnay	Le Chasnay
France	CHU Lille - Institut Cœur Poumon	Lille
France	Centre Hospitalier Saint Joseph Saint Luc	Lyon
France	Hôpital Privé Jacques Cartier	Massy
France	Hôpital Arnaud-de-Villeneuve	Montpellier
France	CMC Ambroise Paré	Neuilly sur seine
France	CHU de Nîmes	Nîmes
France	Groupe Hospitalier Paris Saint Joseph	Paris
France	Hôpital Bichat	Paris
France	Hôpital Cochin	Paris
France	Hôpital européen Georges-Pompidou	Paris
France	Hôpital Henri Mondor	Paris	Ile De France
France	Hôpitaux Universitaires Pitié Salpêtrière	Paris
France	CH Pontoise	Pontoise
France	Centre cardiologique du nord saint denis	Saint-Denis
France	CHU de Strasbourg	Strasbourg
France	Hopital Rangueil	Toulouse
France	CHRU Hôpitaux de Tours	Tours
France	CH Intercommunal de Villeneuve Saint Georges	Villeneuve-Saint-Georges	Villeneuve Saint Georges

Sponsors (1)

Lead Sponsor	Collaborator
CMC Ambroise Paré

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patients not treated with corticosteroids at day 7		7 days
Secondary	Mortality at 28 and 90 days after randomisation		28 and 90 days after randomisation
Secondary	Modification of the cardiac index		7 days
Secondary	Length of stay in intensive care and hospital		28 and 90 days after randomisation
Secondary	Duration of support by catecholamines		28 days after randomisation
Secondary	Clearance of lactatemia		7 days
Secondary	Number of patients use of mechanical ventilation		28 days after randomisation
Secondary	Number of patients with Circulatory assistance		28 days after randomisation
Secondary	Number of patients alive at day 7 without failure (SOFA) score)		7 days
Secondary	Rate of patients with nosocomial infection		28 days after randomisation
Secondary	Rates of patients requiring the introduction of intravenous insulin therapy after randomization		7 days
Secondary	Modification of mean arterial pressure		7 days