Low Dose of Hydrocortisone and Fludrocortisone in Adult Cardiogenic Shock.

NCT ID: NCT03773822

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 380 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-19
• Study Completion Date: 2023-04-05

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.

Conditions

Cardiogenic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

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

Group Type: EXPERIMENTAL

Hydrocortisone + Flucortac

Intervention Type: COMBINATION_PRODUCT

Low dose steroids

Interventions

Hydrocortisone + Flucortac

Low dose steroids

Intervention Type: COMBINATION_PRODUCT

Placebo

Placebo

Intervention Type: OTHER

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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CMC Ambroise Paré

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hôpital Parly II

Le Chesnay, Le Chasnay, France

CH Intercommunal de Villeneuve Saint Georges

Villeneuve-Saint-Georges, Villeneuve Saint Georges, France

Hôpital Ambroise Paré

Boulogne-Billancourt, , France

CH de Marne la Vallée - Site Jossigny

Jossigny, , 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

Hôpitaux Universitaires Pitié Salpêtrière

Paris, , France

Groupe Hospitalier Paris Saint Joseph

Paris, , France

Hôpital Cochin

Paris, , France

Hôpital européen Georges-Pompidou

Paris, , France

Hôpital Bichat

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

Hôpital Henri Mondor

Paris, Île-de-France Region, France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 34980224 (View on PubMed)

Other Identifiers

2018/05

Identifier Type: -

Identifier Source: org_study_id