Clinical trial NCT03773822: Low Dose of Hydrocortisone and Fludrocortisone in Adult Cardiogenic Shock.
Official title: Low Dose of Hydrocortisone and Fludrocortisone in Adult Cardiogenic Shock. A Multicenter, Prospective, Double-blind, Randomized, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiogenic Shock
Keywords: Cardiogenic Shock
Steroids
Hydrocortisone
Fludrocortisone
Reversal of shock
Mortality
Adrenal insufficiency
Lead sponsor: CMC Ambroise Paré
Sponsor class: OTHER
First posted: 2018-12-12
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Patients not treated with corticosteroids at day 7
timeFrame: 7 days
Secondary outcomes:
measure: Mortality at 28 and 90 days after randomisation
timeFrame: 28 and 90 days after randomisation
measure: Modification of the cardiac index
timeFrame: 7 days
measure: Length of stay in intensive care and hospital
timeFrame: 28 and 90 days after randomisation
measure: Duration of support by catecholamines
timeFrame: 28 days after randomisation
measure: Clearance of lactatemia
timeFrame: 7 days
measure: Number of patients use of mechanical ventilation
timeFrame: 28 days after randomisation
measure: Number of patients with Circulatory assistance
timeFrame: 28 days after randomisation
measure: Number of patients alive at day 7 without failure (SOFA) score)
timeFrame: 7 days
measure: Rate of patients with nosocomial infection
timeFrame: 28 days after randomisation
measure: Rates of patients requiring the introduction of intravenous insulin therapy after randomization
timeFrame: 7 days
measure: Modification of mean arterial pressure
timeFrame: 7 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Henri Mondor
state: Ile De France
city: Le Chesnay
country: France
facility: Hôpital Parly II
state: Le Chasnay
city: Villeneuve-Saint-Georges
country: France
facility: CH Intercommunal de Villeneuve Saint Georges
state: Villeneuve Saint Georges
city: Boulogne-Billancourt
country: France
facility: Hôpital Ambroise Paré
city: Jossigny
country: France
facility: CH de Marne la Vallée - Site Jossigny
city: Lille
country: France
facility: CHU Lille - Institut Cœur Poumon
city: Lyon
country: France
facility: Centre Hospitalier Saint Joseph Saint Luc
city: Massy
country: France
facility: Hôpital Privé Jacques Cartier
city: Montpellier
country: France
facility: Hôpital Arnaud-de-Villeneuve
city: Neuilly sur seine
country: France
facility: CMC Ambroise Paré
city: Nîmes
country: France
facility: CHU de Nîmes
city: Paris
country: France
facility: Hôpitaux Universitaires Pitié Salpêtrière
city: Paris
country: France
facility: Groupe Hospitalier Paris Saint Joseph
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital européen Georges-Pompidou
city: Paris
country: France
facility: Hôpital Bichat
city: Pontoise
country: France
facility: CH Pontoise
city: Saint-Denis
country: France
facility: Centre cardiologique du nord saint denis
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Toulouse
country: France
facility: Hopital Rangueil
city: Tours
country: France
facility: CHRU Hôpitaux de Tours
Study officials:
References:
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.