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Hemodynamic and Inflammatory Effects of Abrupt Versus Tapered Corticosteroid Discontinuation in Septic Shock

6 mars 2018 mis à jour par: The Cleveland Clinic
The proposed study will evaluate the potential benefit of a tapered course of hydrocortisone compared to abrupt cessation in patients initiated on hydrocortisone for septic shock. The study will include adult patients in the medical intensive care unit (MICU) who meet criteria for corticosteroid therapy for septic shock according to the current MICU protocol.All patients will receive 7 days of hydrocortisone (50mg/Q6hrs) as part of the routine management of septic shock, before being randomly assigned to receive hydrocortisone taper versus no taper. The primary study endpoint is the incidence of hypotension within 7 days after randomization. Secondary endpoints will include incidence of adrenal insufficiency, and changes in the inflammatory status (assessed by cytokine measurements) before, during, and after corticosteroid discontinuation. The cytokines to be measured include IL-1, IL-6, IL-9, IL-10, and TNF. Since there has not been a randomized clinical trial to investigate the potential benefit of weaning septic patients off low-dose hydrocortisone as opposed to stopping abruptly, this study has potential to change clinical practice by leading to a consistent approach of corticosteroid discontinuation and to a better understanding of their impact on the inflammatory modulation in septic shock.

Aperçu de l'étude

Statut

Résilié

Les conditions

Intervention / Traitement

Description détaillée

Current therapy for septic shock includes antimicrobials, fluid resuscitation, catecholamines, and measures to improve tissue oxygen delivery. The use of corticosteroids as an adjunctive treatment in septic shock has been an area of intensive research over the past decade. A handful of studies suggest that patients in septic shock benefit from low-dose glucocorticoids.Low-dose corticosteroids may improve hemodynamics, decrease vasopressor requirements, and reduce 28-day mortality in patients with vasopressor-refractory septic shock. A meta-analysis from 2004 also suggested that the use of low-dose corticosteroids does not significantly increase the risk of superimposed infections, gastrointestinal bleeding, or hyperglycemia.

The exact mechanism for this beneficial effect has not been completely established, although direct vascular effects and anti-inflammatory effects of corticosteroids have been proposed. While there is ongoing debate over which subpopulations of patients derive benefit from corticosteroids, there is as much controversy regarding the appropriate duration of therapy. The current Surviving Sepsis Campaign suggests that intravenous IV hydrocortisone 200-300mg/day should be given to adult septic shock patients after it has been confirmed that their blood pressure is poorly responsive to fluid resuscitation and vasopressor therapy. The duration of therapy is not specified. There is also no clear evidence to suggest that patients benefit from tapering steroids as opposed to stopping them abruptly; both strategies have been employed. Annane showed both a mortality benefit and shorter duration of vasopressor therapy with an abrupt end to a 7-day course of hydrocortisone and fludrocortisone in patients with septic shock compared to placebo; while others showed a similar benefit with a taper.Keh demonstrated reversal of both hemodynamic and immunologic effects after a three-day treatment of "low-dose" hydrocortisone, suggesting that some of the beneficial effects of steroids disappear in less than 24 hours. Interestingly, 30% of patients had to restart vasopressor therapy after discontinuation of corticosteroids in one of the Keh's study arms.

Type d'étude

Interventionnel

Inscription (Réel)

11

Phase

  • Phase 4

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • États-Unis
    • Ohio
      • Cleveland, Ohio, États-Unis, 44195
        • Cleveland Clinic

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 99 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:Patients who meet the following criteria will be enrolled in the study:

  • suspected septic shock
  • initiation of hydrocortisone 50mg IV Q6H (per MICU protocol)
  • written informed consent signed by patient or legal surrogate
  • Septic shock is defined by meeting all of the following requirements:

  • Clinical evidence of infection. Clinical evidence of infection is defined as the presence of a known or probable source of infection that has necessitated the initiation of systemic antimicrobial therapy. Clinical evidence of infection could include (but is not limited to) one or more of the following:

    1. presence of increased number of PMNs (neutrophils) in normally sterile body fluid
    2. positive culture or gram stain of blood, sputum, urine, or normally sterile body for a pathogenic microorganism
    3. chest radiograph consistent with a diagnosis of pneumonia with a positive culture, gram stain, diagnostic bronchoalveolar lavage, or protected specimen brush for a respiratory tract pathogen
    4. focus of infection identified by visual inspection (e.g., ruptured bowel found at surgery, wound with purulent drainage, radiographic or Computed tomographic evidence of an abscess or osteomyelitis, etc.) and
    5. patient has an underlying disease or condition that is highly likely to be associated with infection (e.g., ascending cholangitis, ischemic bowel, etc.)

  • Two of the following:

    1. Core temperature either > 38°C (> 100.4°F) or < 36°C (< 96.8°F)
    2. Tachycardia. Heart rate greater > 90 beats/minute
    3. Respiratory rate > 20 b/min or PaCO2 < 32 torr, or need for mechanical ventilation due to sepsis
    4. WBC > 12 or < 4 K/mm3
  • End-organ cardiovascular dysfunction defined as hypotension unresponsive to fluid replacement necessitating vasopressor therapy, or lactate ≥4 mmol/L

Exclusion Criteria:

  • age less than 18
  • previous systemic corticosteroid therapy in the past 90 days (prednisone >5 mg/d or equivalent)
  • pregnancy
  • Acquired Immune Deficiency Syndrome (AIDS)
  • hematological malignancies
  • advanced form of cancer with less than 30-day life expectancy
  • patients who receive fludrocortisone
  • evidence of prior acute myocardial infarction

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: hydrocortisone
Hydrocortisone 50 mg IV every 12 hours x 4 doses (2 days), followed by Hydrocortisone 50 mg IV every 24 hours x 2 doses (2 days)
Médicament: hydrocortisone
1) Hydrocortisone 50 mg IV every 12 hours x 4 doses (2 days), followed by Hydrocortisone 50 mg IV every 24 hours x 2 doses (2 days)
Autres noms:
  • 11β,17α,21-trihydroxypregn-4-ene-3,20-dione
Médicament: Normal Saline
0.9% sodium chloride (equal volume to hydrocortisone) IV every 12 hours x 4 doses (2-days), followed by 0.9% sodium chloride (equal volume to hydrocortisone) IV every 24 hours x 2 doses (2-days)
Autres noms:
  • 0,9 % de chlorure de sodium
Comparateur placebo: Normal Saline (placebo)
0.9% sodium chloride (equal volume to hydrocortisone) IV every 12 hours x 4 doses (2-days), followed by 0.9% sodium chloride (equal volume to hydrocortisone) IV every 24 hours x 2 doses (2-days)
Médicament: Normal Saline
0.9% sodium chloride (equal volume to hydrocortisone) IV every 12 hours x 4 doses (2-days), followed by 0.9% sodium chloride (equal volume to hydrocortisone) IV every 24 hours x 2 doses (2-days)
Autres noms:
  • 0,9 % de chlorure de sodium

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Incidence of Hypotension Between Study Days 8 and 14 (Within 7 Days of the Initiation of Study Drug).
Délai: Day 14
Study screening/enrollment stopped due to lack of eligible subjects. No outcome measures were analyzed due to the low enrollment.
Day 14

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

The Cleveland Clinic

Les enquêteurs

  • Chercheur principal: Jorge A Guzman, MD, The Cleveland Clinic

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 mai 2008

Achèvement primaire (Réel)

1 août 2010

Achèvement de l'étude (Réel)

1 août 2010

Dates d'inscription aux études

Première soumission

21 juin 2010

Première soumission répondant aux critères de contrôle qualité

24 juin 2010

Première publication (Estimation)

25 juin 2010

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

2 avril 2018

Dernière mise à jour soumise répondant aux critères de contrôle qualité

6 mars 2018

Dernière vérification

1 mars 2018

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 08-336

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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