VITAMINS Trial: Vitamin C, hydrocortisone, and thiamine in Septic Shock

vitamins trial visual summary

2021 2021 VITAMINS TRIAL M Effect of Vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock Open label, multi-centre, randomized, phase IIb clinical trial Objective: To investigate whether treatment with Vitamin C, hydrocortisone & thiamine (intervention) lead to a more rapid resolution of septic shock compared with hydrocortisone alone (control) 211 Inclusion criteria: patients had suspected or documented infection with an acute increase of at least 2 points in the SOFA score, had a lactate level > 2 mmol/L, and were vasopressor dependent for at least 2 hours. patients Intervention group (n = 107) Control group (n = 104) PRIMARY OUTCOME 122.1 Time alive and free of vasopressors (in hours) Diff -0.6; 95% CI, -8.3 to 7.2; P=0.83 124.6 SECONDARY OUTCOME Change in SOFA score at day 3 Diff -0.1; 95% CI, -1.9 to -0.1; P=0.02 24 28-days mortality % Diff 2.3; 95% CI, -8.9 to 13.4; P=0.69 21 Conclusion: In patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. T Fujii et al. JAMA 2020;323(5):423-431

ARREST Trial: ECMO-facilitated Resuscitation in Refractory Cardiac Arrest

arrest trial ecmo cardiac arrest

2020 ARREST 2020 TRIAL M Advanced reperfusion strategies for patients with out-of hospital cardiac arrest (OHCA) and refractory ventricular fibrillation (VF) Phase 2, single center, open-label, randomized clinical trial Objective: To compare implementation of early ECMO facilitated resuscitation compared to standard ACLS resuscitation in adults suffering out of hospital cardiac arrest (OHCA) presenting with an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT) 30 patients Patients 18 to 75 years of age with initial rhythm of VF or pulseless VT; no return of spontaneous circulation (ROSC) after 3 shocks; body habitus able to support mechanical CPR; estimated transport time < 30 minutes ACLS group (n=15) ECMO-facilitated group (n=15) PRIMARY OUTCOME Survival to hospital discharge % Diff. 36.2;95% CI 3.7 to 59.2, NNT 3 (1.5 – 13.6) Posterior probability of ECMO superiority 0.9861 SECONDARY OUTCOME Cumulative survival HR 0-16, 95% CI 0.06 to 0-41;P<0.0001 Total adverse events 166 Conclusion: Early ECMO-facilitated resuscitation for patients with OHCA and refractory ventricular fibrillation significantly improved survival to hospital discharge compared with standard ACLS treatment. D Yannopoulos et al. The Lancet 2020

SURMOUNT-1 Trial: Tirzepatide for Weight Loss in Obesity

surmount 1 trial tirzepatide obesity

2022 SURMOUNT-1 TRIAL M Tirze patide Once Weekly for the Treatment of Obesity Phase 3 double-blind, randomized, controlled trial Objective: To assess the efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and GLP-1 agonist, in treatment of obesity 2539 Adults with a body-mass index (BMI) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes tirzepatide (5 mg, 10 mg, or 15 mg) (N=1896) VS Placebo (N=643) (PRIMARY OUTCOME -20.9 percentage change in body weight (15mg dose) % P<0.001 -3.1 91 weight reduction of at least 5% (15mg dose) P<0.001 Tirzepatide showed benefit across all dosages when compared to placebo SECONDARY OUTCOME 6.2 Adverse events caused treatment discontinuation (15mg dose) % 2.6 Conclusion: In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. Ania M. Jastreboff, et al. NEJM, 2022; 387:205-216

MR CLEAN-NO IV Trial Summary: IV Alteplase before Endovascular Therapy in Stroke

mr clean no iv trial alteplase stroke

2021 MR CLEAN-NO IV TRIAL M 2021 A Randomized Trial of Intravenous Alteplase before Endovascular Treatment(EVT) for Stroke investigator-initiated, international, multicenter, prospective, randomized, open-label trial ” d Objective: To determine whether EVT alone would be more effective, or noninferior, as compared with intravenous alteplase followed by EVT in European patients with acute ischemic stroke due to an intracranial anterior-circulation stroke 539 Participants > 18 years with occlusion of the intracranial segment of the ICA and/or of the 1st or proximal 2nd segment of the MCA confirmed by CTA & eligible for IV alteplase (<4.5 hrs); CT/MRI ruling out Intracranial hhg; Neurologic deficit as indicated by NIHSS score of 2. patients EVT alone (n=273) Alteplase followed by EVT (n=266) PRIMARY OUTCOME Modified Rankin scale at 90 days OR 0.84; 95% CI, 0.62 to 1.15; P=0.28 SECONDARY OUTCOME 20.5 Mortality % OR 1.39; 95% CI, 0.84 to 2.30 15.8 5.9 Symptomatic intracerebral hemorrhage % OR 1.30; 95% CI, 0.60 to 2.81 5.3 Conclusion: EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. NE LeCouffe et al. NEJM 2021;385:1833-1844

KEYNOTE-826 Trial Summary: Pembrolizumab in Metastatic Cervical Cancer

keynote 826 trial pembrolizumab cervical cancer

2021 KEYNOTE-826 TRIAL Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer double-blind, phase 3, randomized controlled trial Objective: To assess whether adding pembrolizumab to platinum-based chemotherapy with or without bevacizumab would improve efficacy as compared with chemotherapy with or without bevacizumab as first-line therapy for persistent, recurrent, or metastatic cervical cancer 617 patients Participants 18 years of age with persistent, recurrent, or metastatic adenocarcinoma, adenosquamous carcinoma, or squamous-cell carcinoma of cervix that had not been treated with systemic chemotherapy and was not amenable to curative treatment Pembrolizumab (n=308) Placebo (n=309) PRIMARY & SECONDARY OUTCOME PD-L1 combined positive score > 1 10.4 8.2 Progression-free survival (months) HR 0.62; 95%CI 0.50-0.77; P<0.001 53.0 Overall survival at 24M HR 0.64; 95%CI 0.50-0.81; P<0.001 41.7 PD-L1 combined positive score > 10 10.4 Progression-free survival (months) HR 0.58; 95%CI 0.44-0.77; P<0.001 8.1 54.4 Overall survival at 24M HR 0.61; 95%CI 0.44-0.84; P=0.001 44.6 Grade 3 to 5 adverse events % 30.3 Anemia 26.9 Neutropenia 12.4 9.7 Conclusion: Progression-free & overall survival were significantly longer with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic cervical cancer who were also receiving chemotherapy with or without bevacizumab. N Colombo et al. NEJM 2021;385:1856-1867

EMPULSE Trial Summary: Empagliflozin in Acute Heart Failure

empulse trial empagliflozin heart failure

2021 EMPULSE TRIAL Empagliflozin in patients hospitalized for Acute Heart Failure Randomized, parallel trial Objective: To evaluate empagliflozin compared with placebo among patients with acute decompensated heart failure. 530 patients Inclusion criteria: Patients hospitalized for acute HF regardless of ejection fraction or diabetes status & following stabilization criteria; NT-proBNP >1600 pg/ml or BNP 2400 pg/ml during hospitalization or within 72 hours prior to admission Empagliflozin group (n = 265) Placebo group (n = 265) PRIMARY OUTCOME 53.9 Clinical benefit at 90-days % P=0.0054 39.7 SECONDARY OUTCOME 4 All-cause mortality % 8.3 10.6 Heart failure events % 14.7 7.7 Acute renal failure % 12.1 Conclusion: Among patients with acute decompensated HF, empagliflozin was associated with significant clinical benefit at 90 days with fewer deaths, improvement in quality of life & greater reduction in body weight. There were no safety concerns with empagliflozin. Presented by Dr.A.A.Voors at the AHA’s Scientific Sessions, November 14, 2021

AVATAR Trial Summary: AVR in Asymptomatic Severe Aortic Stenosis

AVATAR Trial AVR aortic stenosis

2021 AVATAR TRIAL M Aortic Valve replacement versus Conservative treatment in asymptomatic severe Aortic Stenosis Parallel, Randomised controlled trial Objective: To evaluate aortic valve replacement (AVR) compared with conservative therapy among patients with asymptomatic severe aortic stenosis 157 Inclusion criteria: Patients 18 years of age with asymptomatic severe aortic stenosis (asymptomatic status confirmed by exercise testing) & Society of Thoracic Surgeons-Predicted Risk of Mortality (STS-PROM) score <8% patients Early surgery group(n=78) Conservative therapy group (n=79) PRIMARY OUTCOME 15.2 All-cause death % HR 0.46; 95% CI, 0.23 to 0.90; P=0.02 34.7 SECONDARY OUTCOME Thirty-day mortality % OR 0.34; 95% CI, 0.02 to 5.61 9.5 Heart failure hospitalization % HR 0.32; 95% CI, 0.08 to 1.19 20.1 Conclusion: Among patients with asymptomatic severe aortic stenosis, early surgery was beneficial. Early surgery compared with conservative therapy was associated with a significantly lower incidence of composite adverse events over a median follow-up of 32 months. M Banovic et al. CIRCULATIONAHA.121.057639

PALACS Trial Summary: Posterior Left Pericardiotomy for Post-op AFib

PALACS trial pericardiotomy afib

2021 PALACS TRIAL M Posterior left pericardiotomy for the prevention of postoperative atrial fibrillation after cardiac surgery Randomized, parallel, stratified, single-centre study Objective: To evaluate posterior left pericardiotomy compared with no intervention among patients undergoing open heart surgery 420 patients Patients 18 years of age,undergoing elective interventions on the coronary arteries, aortic valve or ascending aorta, or a combination of these & no h/o atrial fibrillation or other arrhythmias or contraindications to the experimental intervention Posterior left pericardiotomy (n = 212) No intervention (n = 208) PRIMARY OUTCOME 18 Postoperative atrial fibrillation % OR 0.44; 95% CI, 0-27 to 0-70; P=0.0005 SECONDARY OUTCOME Major adverse events % Pericardial effusion % RR 0.58; 95% CI, 0-37 to 0.91; P=0.46 Conclusion: Among patients undergoing open heart surgery for CABG, aortic valve replacement, and/or aortic repair, posterior left pericardiotomy was beneficial. Pericardiotomy was associated with a significant reduction in postoperative atrial fibrillation, without increasing the incidence of complications.. M Gaudino et al. The Lancet, 398(10316), 2075-2083

ANTHARTIC Trial Summary: Prevention of Ventilator-Associated Pneumonia after Cardiac Arrest

ANTHARTIC Trial pneumonia cardiac arrest

2019 ANTHARTIC TRIAL M Prevention of early Ventilator-Associated Pneumonia after cardiac arrest Multicentre, randomised, double-blind, placebo-controlled Objective: To investigate whether in post out-of-hospital cardiac arrest (OOHCA) patients treated with targeted temperature management, does the use of empirical antibiotics prevent early ventilator-associated pneumonia. 194 patients Inclusion criteria: Patients > 18 years of age hospitalized in the ICU after OOHCA with shockable rhythm,& treated with targeted temperature management of 32 to 34°C Antibiotic Group (N=99) Control Group (N=95) PRIMARY OUTCOME Rate of early ventilator-associated pneumonia % HR 0.55; 95% CI, 0.31 to 0.92; P=0.003 SECONDARY OUTCOME Rate of late VAP % Urinary tract infection % Conclusion: A 2-day course of antibiotic therapy with amoxicillinclavulanate in patients receiving a 32-to-34°C targeted temperature management strategy after out-of-hospital cardiac arrest with initial shockable rhythm resulted in a lower incidence of early ventilator associated pneumonia than placebo. B François et al. NEJM 2019,381:1831-42

Beta Blockers in Traumatic Brain Injury Trial Summary

Beta blockers traumatic brain injury

2020 BETA-BLOCKER THERAPY IN TBI Beta-Blocker Therapy in Severe Traumatic Brain Injury (TBI) Single-center,non-blinded,randomized controlled trial d d Objective: To examine the effect of beta-blockers on outcomes in TBI patients. 154 patients Patients > 18 years with: -blunt head trauma & an intracranial injury with an AIS score of 3-5 requiring a surgical intervention within 24hrs of admission -admitted to the Neuro-ICU with severe TBI detected on admission CT or GCS score of <12. Beta-blocker therapy (n=86) No Beta-blocker therapy (n=68) PRIMARY OUTCOME 18.6 Relative lower In-hospital mortality % Diff 1; 95% CI, -10.4 to 12.3; P=0.012 44 SECONDARY OUTCOME 66.7 Glasgow Outcome Scale-Extended (GOS-E) >5 at discharge RR 1; 95% CI, 0.9 to 1.2; P=0.8 72.4 77.5 GOS-E >5 at 6 months RR 1; 95% CI, 0.9 to 1.2; P=0.3 86.5 Conclusion: Early Propranolol decreases in-hospital mortality and improves long-term functional outcome in isolated severe TBI. This randomized trial speaks in favor of routine administration of beta-blocker therapy as part of a standardized neurointensive care protocol. H Khalili et al. World J Surg (2020) 44:1844-1853