- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00427388
Steroids In caRdiac Surgery Trial (SIRS Trial)
Phase IV Study of Perioperative Steroid's Effects on Death or MI in High-Risk Patients Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
Cardiopulmonary bypass (CPB) is a commonly performed surgical procedure with over 500,000 per year in North America. CPB initiates a systemic inflammatory response characterized by both cell and protein activation. Platelets, neutrophils, monocytes, macrophages, coagulation, fibrinolytic, and kallikrein cascades all take part in what results in increased endothelial permeability, vascular, and parenchymal damage. These inflammatory pathways facilitate development of post-operative complications including thrombosis, myocardial injury and infarction, respiratory failure, renal and neurological dysfunction, bleeding disorders, altered liver function and ultimately, multiple organ failure.
In an attempt to minimize the deleterious effects of CPB, investigators have tested a variety of strategies in cardiac surgery ranging from the complete avoidance of CPB, to the use of biocompatible circuits and pharmacologic agents to abrogate the systemic response. Investigators have consistently demonstrated the efficacy of steroids as the most potent anti-inflammatory agent for use during CPB. In fact, from the available evidence, the 2004 AHA guidelines for coronary artery bypass grafting (CABG) "support liberal prophylactic use in patients undergoing extracorporeal circulation". However, the trials that do exist within this literature are focused on biochemical endpoints and are insufficiently powered to make conclusions on hard clinical endpoints. Our pilot RCT, SIRS I, demonstrated the efficacy of a low dose steroid protocol in the suppression of this inflammatory cascade. We hypothesize that this low dose protocol will yield clinical benefit while avoiding the potential adverse effects of steroids which are known to be dose dependent.
The primary aim of the SIRS trial is to determine if perioperative pulse dose Methylprednisolone results in improved early survival and less myocardial infarction in cardiac surgery requiring CPB. Additional secondary aims of the SIRS trial are to determine the effect of steroids on other clinical outcomes including length of stay, new onset atrial fibrillation, transfusion requirements, infectious, wound, and gastrointestinal complications.
The design of the SIRS trial is a prospective multicentre international double-blind placebo controlled randomized clinical trial. The sample size of 7500 patients will have 80% to 90% power to detect a 20-30% RRR for the primary outcome with an α=0.05 (two-sided), anticipating a 6% rate of death in the control arm. Our aim is to have 85 international centers participate which, recruiting at 5 patients per month, would complete recruitment in 36 months. This will be a large trial with a simple design and objective outcomes.
A sub-group of patients will be enrolled in a renal sub-study. This sub-study will determine if the risk of acute kidney injury is lower in patients treated with intravenous steroid versus placebo, if steroids lead to better preservation of kidney function six months after cardiac surgery, and whether the impact of steroid exposure differs in patients with and without pre-operative chronic kidney disease.
Type d'étude
Inscription (Réel)
Phase
- Phase 4
Contacts et emplacements
Lieux d'étude
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Ontario
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Hamilton, Ontario, Canada, L8L 2X2
- Hamilton General Hospital
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-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Age greater than 18 years
- Require CPB for any cardiac surgical procedure (such as CABG, Valve, Aorta, or combined procedures)
- Must have a EuroSCORE ≥ 6
- Provide written informed consent
NOTE: For participating sites in India, China and Hong Kong, the following eligibility criteria will be applied:
- Age greater than 18 years
- Require CPB for any cardiac surgical procedure (such as CABG, Valve, Aorta, or combined procedures)
Must have at least one of the following:
- EuroSCORE greater than or equal to 4 and undergoing valvular surgery
- EuroSCORE greater than or equal to 6 and undergoing any other cardiac surgery procedure (i.e. CABG, Aorta)
- Provide written informed consent
Exclusion Criteria:
- Use of systemic corticosteroids
- History of bacterial or fungal infection in last 30 days
- Allergy/intolerance to corticosteroids
- Will receive Aprotinin
- Previous participation in study
Plan d'étude
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: Treatment
500 mg of methylprednisolone divided into two intravenous doses of 250 mg each, one during anesthetic induction and the other on CPB initiation
|
Given by IV in 2 doses (250 mg each dose for a total of 500 mg)
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Comparateur placebo: Placebo
500 mg of matching placebo (normal saline solution) divided into two intravenous doses of 250 mg each, one during anesthetic induction and the other on CPB initiation
|
Given in 2 IV doses (approximately 4 ml of 0.9% normal saline solution in each dose)
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Mortality at 30 days
Délai: 30 days post-randomization
|
30 days post-randomization
|
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Composite
Délai: 30 days post-randomization
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Incidence of the composite outcome of death, myocardial infarction, stroke, renal failure (KDIGO Stage III acute kidney injury, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines), or respiratory failure within 30 days
|
30 days post-randomization
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
MI or Mortality at 30 days
Délai: 30 days post-randomization
|
Composite of death or significant myocardial infarction within 30 days post-randomization
|
30 days post-randomization
|
Mortality at 6 months
Délai: 6 months post-randomization
|
All-cause mortality at 6 months post-randomization
|
6 months post-randomization
|
Atrial Fibrillation
Délai: 30 days post-randomization
|
New onset atrial fibrillation within 30 days post-randomization
|
30 days post-randomization
|
Transfusion Requirements
Délai: 24 hours post-surgery
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Transfusion requirements within first 24 hours post-operative
|
24 hours post-surgery
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Chest Tube Output
Délai: 24 hours post-surgery
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Chest tube output within first 24 hours post-operative
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24 hours post-surgery
|
ICU and Hospital Length of Stay
Délai: Hospital Discharge
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Length of ICU stay and hospital stay
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Hospital Discharge
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Infection
Délai: 30 days post-randomization
|
Infection within 30 days post-randomization
|
30 days post-randomization
|
Delirium
Délai: 3 days post-surgery
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Delirium at day 3 post-operative
|
3 days post-surgery
|
Wound Complication
Délai: 30 days post-randomization
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Wound complication within 30 days post-randomization
|
30 days post-randomization
|
GI Hemorrhage
Délai: 30 days post-randomization
|
GI hemorrhage or GI perforation within 30 days post-randomization
|
30 days post-randomization
|
Insulin Use
Délai: 24 hours post-surgery
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Post-operative insulin use within the first 24 hours after surgery
|
24 hours post-surgery
|
Peak Blood Glucose
Délai: 24 hours post-surgery
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Peak blood glucose within the first 24 hours after surgery
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24 hours post-surgery
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Salim Yusuf, MD, DPhil, PHRI
- Chercheur principal: Kevin Teoh, MD, MSc, McMaster University
- Chercheur principal: Richard P Whitlock, MD, MSc, McMaster University
Publications et liens utiles
Publications générales
- Garg AX, Vincent J, Cuerden M, Parikh C, Devereaux PJ, Teoh K, Yusuf S, Hildebrand A, Lamy A, Zuo Y, Sessler DI, Shah P, Abbasi SH, Quantz M, Yared JP, Noiseux N, Tagarakis G, Rochon A, Pogue J, Walsh M, Chan MT, Lamontagne F, Salehiomran A, Whitlock R; SIRS Investigators. Steroids In caRdiac Surgery (SIRS) trial: acute kidney injury substudy protocol of an international randomised controlled trial. BMJ Open. 2014 Mar 5;4(3):e004842. doi: 10.1136/bmjopen-2014-004842.
- Whitlock RP, Young E, Noora J, Farrokhyar F, Blackall M, Teoh KH. Pulse low dose steroids attenuate post-cardiopulmonary bypass SIRS; SIRS I. J Surg Res. 2006 May 15;132(2):188-94. doi: 10.1016/j.jss.2006.02.013. Epub 2006 Mar 29.
- Whitlock RP, Rubens FD, Young E, Teoh KH. Pro: Steroids should be used for cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2005 Apr;19(2):250-4. doi: 10.1053/j.jvca.2005.02.010. No abstract available.
- Whitlock R, Teoh K, Vincent J, Devereaux PJ, Lamy A, Paparella D, Zuo Y, Sessler DI, Shah P, Villar JC, Karthikeyan G, Urrutia G, Alvezum A, Zhang X, Abbasi SH, Zheng H, Quantz M, Yared JP, Yu H, Noiseux N, Yusuf S. Rationale and design of the steroids in cardiac surgery trial. Am Heart J. 2014 May;167(5):660-5. doi: 10.1016/j.ahj.2014.01.018. Epub 2014 Mar 1.
- Garg AX, Chan MTV, Cuerden MS, Devereaux PJ, Abbasi SH, Hildebrand A, Lamontagne F, Lamy A, Noiseux N, Parikh CR, Perkovic V, Quantz M, Rochon A, Royse A, Sessler DI, Shah PJ, Sontrop JM, Tagarakis GI, Teoh KH, Vincent J, Walsh M, Yared JP, Yusuf S, Whitlock RP; SIRS Investigators. Effect of methylprednisolone on acute kidney injury in patients undergoing cardiac surgery with a cardiopulmonary bypass pump: a randomized controlled trial. CMAJ. 2019 Mar 4;191(9):E247-E256. doi: 10.1503/cmaj.181644.
- Theriault S, Whitlock R, Raman K, Vincent J, Yusuf S, Pare G. Gene Expression Profiles for the Identification of Prevalent Atrial Fibrillation. J Am Heart Assoc. 2017 Jun 30;6(7):e006057. doi: 10.1161/JAHA.117.006057.
- Whitlock RP, Devereaux PJ, Teoh KH, Lamy A, Vincent J, Pogue J, Paparella D, Sessler DI, Karthikeyan G, Villar JC, Zuo Y, Avezum A, Quantz M, Tagarakis GI, Shah PJ, Abbasi SH, Zheng H, Pettit S, Chrolavicius S, Yusuf S; SIRS Investigators. Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Sep 26;386(10000):1243-1253. doi: 10.1016/S0140-6736(15)00273-1.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Anticipé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Processus pathologiques
- Inflammation
- Choc
- Syndrome de réponse inflammatoire systémique
- Effets physiologiques des médicaments
- Agents autonomes
- Agents du système nerveux périphérique
- Agents anti-inflammatoires
- Agents antinéoplasiques
- Antiémétiques
- Agents gastro-intestinaux
- Glucocorticoïdes
- Les hormones
- Hormones, substituts hormonaux et antagonistes hormonaux
- Agents antinéoplasiques, hormonaux
- Agents neuroprotecteurs
- Agents protecteurs
- Prednisolone
- Acétate de méthylprednisolone
- Méthylprednisolone
- Hémisuccinate de méthylprednisolone
- Acétate de prednisolone
- Hémisuccinate de prednisolone
- Phosphate de prednisolone
Autres numéros d'identification d'étude
- SIRS 2007
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