RECONNECT Trial Summary: Mechanical Ventilation After Successful Spontaneous Breathing Trial

2017 RECONNECT TRIAL Reconnection to mechanical ventilation (MV) for 1h after a successful spontaneous breathing trial (SBT) reduces reintubation in critically ill patients. Parallel, two-arm, prospective randomised controlled trial Objective: To evaluate the reduction in need for reintubation in critically ill patients who pass a SBT by 1-hour rest compared with immediate extubation (control) 470 Inclusion criteria: ICU patients aged > 18 years who received invasive MV for 12 hours were screened daily and followed prospectively (while undergoing serial SBTS) until they successfully completed an SBT patients 1-hr REST by reconnecting to MV (n=227] ON Immediate extubation (n=243] PRIMARY OUTCOME Re-intubation within 48h % OR 0.33; 95% CI 0.16-0.65; P<0.001 SECONDARY OUTCOME Post extubation Resp. failure within 48h % 24 OR 0.35; P<0.001 No difference in length of ICU or hospital stay or mortality Conclusion: 1-hr rest after a successful SBT reduces reintubation and post extubation respiratory failure in critically ill patients. MM Fernandez et al. Intensive Care Med 2017 Nov;43(11):1660-1667 Summary by Dr. Shreyash Bhoyar, MBBS

LOVIT Trial Summary: IV Vitamin C in Septic Shock

LOVIT Trial summary iv vitamin c in sepsis shock ICU

2022 LOVIT TRIAL Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit Randomized, placebo-controlled trial Objective: To assess the use of intravenous vitamin C in a dults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) 872 patients 872 Inclusion Criteria: adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor ore to IV vitamin C DH (N=435) Placebo (N=437) PRIMARY OUTCOMES 44.5 Composite of death or persistent organ dysfunction on day-28 % Risk ratio, 1.21 (95% CI) 1.04 to 1.40; P=0.01 38.5 SECONDARY OUTCOMES 35.4 Death by day 28 % Risk ratio, 1.17; 95% CI, 0.98 to 1.40 31.6 9.1 Persistent organ dysfunction by day 28 % Risk ratio, 1.30; 95% CI, 0.83 to 2.05 6.9 Conclusion: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. François Lamontagne, et al. NEJM June 15, 2022, DOI: 10.1056/NEJMoa2200644 M Visualmed

Early Palliative Care in Patients with Lung Cancer Trial

early palliation in lung cancer clinical trial

2010 EARLY PALLIATIVE CARE M Early Palliative Care for Patients with Metastatic Non-Small-cell Lung Cancer Single-center, Prospective, non-blinded, parallel-group, randomized, control Objective: In patients with metastatic NSCLC, how does the early introduction of palliative care affect the quality of life? 151 patients Inclusion Criteria: Ambulatory Patients with pathologic diagnosis of NSCLC in prior 8 weeks. ECOG performance status 0-2. Early palliative care (N=77) Standard Care (N=74) PRIMARY OUTCOME 2.3 Trial Outcome Index (TOM) (difference between groups 4.6, 95% CI, 0.2 to 8.9, P=0.04) -2.3 SECONDARY OUTCOME 11.6 Median Survival (months) (HR 1.7, 95% CI 1.14-2.54, p=0.02) 8.9 53 Documentation of Resuscitation Preferences (%) P=0.05 28 Aggressive end-of-life care (%) P=0.05 54 Conclusion: Early integration of palliative care improved quality of life, reduced aggressive care at the end of life, and improved survival among patients with metastatic NSCLC. Temel JSet al. NEJM. 2010;363(8):733-742. Summary by Kiriti S. Vattikonda DO

ACTION Trial: Anticoagulation in COVID-19

ACTION Trial anticoagulation covid 19

2021 ACTION TRIAL Therapeutic vs. prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer Pragmatic, open-label (with blinded adjudication), multicentre, randomised Objective: to evaluate therapeutic anticoagulation compared with prophylactic anticoagulation among patients admitted with coronavirus disease 2019 (COVID-19) infection. 615 patients Inclusion Criteria: Patients (aged >18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had symptoms for up to 14 days before randomisation Therapeutic anticoagulation (N = 311) Prophylactic anticoagulation (N = 304) . PRIMARY OUTCOME 34.8 Hierarchical analysis of mortality, duration of hospitalization, and duration of oxygen use% P = nonsignificant 41.3 SECONDARY OUTCOME 11.3 All-cause mortality % P = nonsignificant 7.6 3.5 Venous thromboembolism % P = nonsignificant 5.9 8.4 ISTH major bleeding % P<0.05 2.3 Conclusion: In patients hospitalised with COVID-19 and elevated D-dimer, inhospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation Lopes RD et al. Lancet 2021:397:2253-63.

POISE-3 Trial Summary: Tranexamic Acid in Noncardiac Surgery

POISE 3 trial tranexamic acid noncardiac surgery

2022 POISE-3 TRIAL МІ Tranexamic Acid in Patients Undergoing Noncardiac Surgery International, randomized, controlled trial Objective: In patients undergoing noncardiac surgery who are at risk for bleeding and CV events, does tranexamic acid lowers incidence of major bleeding when compared to placebo and is it noninferior to placebo with respect to the incidence of major CV complications within 30 days? 9535 Inclusion Criteria: Patients (aged >45 years) undergoing inpatient noncardiac surgery, and were at risk for bleeding and CV complications (e.g., known atherosclerotic disease, undergoing major surgery, >70 years age, and a serum Cr >2.0 mg/dl patients Tranexamic acid (1-g IV bolus) (N = 4757) Placebo (N = 4778) PRIMARY OUTCOMES 9.1 Life-threatening bleeding, major bleeding, or bleeding into a critical organ at 30 days % HR 0.76; 95% CI, 0.67 to 0.87; P<0.001 for superiority 11.7 14.2 MI, nonhemorrhagic stroke, Arterial thrombosis, or symptomatic proximal VTE% HR 1.02; 95% CI, 0.92 to 1.14; P=0.04 for noninferiority 13.9 SECONDARY OUTCOME 1.4 Myocardial infarction % HR 1.27; 95% CI, 0.89–1.82 20.7 Net risk-benefit outcome % HR 0.94; 95% CI, 0.86–1.02 21.9 Conclusion: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. Devereaux PJ, et al. NEJM April 2, 2022, DOI: 10.1056/NEJMoa2201171

CHAP Trial Summary: Chronic Hypertension in Pregnancy

CHAP Trial: Treating chronic HTN in pregnancy

2022 CHAP TRIAL Treatment for Mild Chronic Hypertension during Pregnancy Open-label, multicenter, randomized trial Objective: To assess if treating mild chronic hypertension during pregnancy with a BP goal of <140/90 mmHg would lower incidence of adverse maternal and perinatal outcomes than a strategy of withholding treatment until the BP was 160/105 mm Hg or higher 2408 Inclusion Criteria: Pregnant women with a known or new dx of chronic HTN and a viable singleton fetus before 23 weeks’ gestation. New chronic HTN was defined as a SBP of > 140 mmHg, a DBP of > 90 mm Hg, or both on > 2 occasions > 4 hours apart before 20 weeks’ gestation in patients without chronic HTN patients Active Treatment (N=1208) Control (N=1200) PRIMARY OUTCOMES 30.2 Preeclampsia, preterm birth < 35 weeks, placental abruption, fetal or neonatal death Risk ratio (95% CI) 0.82 (0.73–0.92); P < 0.001 37.0 11.2 Small-for-gestational-age birth weight below the 10th percentile for gestational age % Risk ratio (95% CI) 1.07 (0.85-1.36), P = 0.56 10.4 SECONDARY OUTCOME 2.1 Composite maternal cardiovascular complications % 0.75 (0.45 to 1.26) 2.8 Conclusion: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. Alan T. Tita, et al. NEJM April 2, 2022, DOI: 10.1056/NEJMoa2201295

DISCHARGE Trial Summary: CT or Angio in Stable Chest Pain

DISCHARGE Trial Summary: CT or coronary angiogram in stable angina

2022 DISCHARGE TRIAL Summary: CT or Invasive Coronary Angiography in Stable Chest Pain- Pragmatic, randomized controlled trial- Objective: To evaluate computed tomography (CT) compared with invasive coronary angiography among patients with stable chest pain and intermediate pretest probability of obstructive coronary artery disease- 3561 patients- Inclusion Criteria: -At least 30 years of age -Stable chest pain -Intermediate pretest probability of obstructive CAD ст (n = 1,808) ICA (n = 1,753)- A PRIMARY OUTCOMES 2.1 CV death, nonfatal MI, or nonfatal stroke % HR 0.70; 95% CI, 0.46 to 1.07; P=0.10 3.0 SECONDARY OUTCOME 0.5 Major procedure-related complications % HR 0.26; 95% CI, 0.13 to 0.55 8.8 Angina during the final 4 wks of follow-up% OR 1.17; 95% CI, 0.92 to 1.48 7.5 Conclusion: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. The DISCHARGE Trial Group. N Engl J Med 2022;Mar 4:[Epub ahead of print].

UK TAVI Trial Summary: TAVI in Moderate Aortic Stenosis

UK TAVI aortic stenosis trial summary

2022 UK TAVI TRIAL M Effect of TAVI vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients With Aortic Stenosis Multicenter, randomized controlled trial – Objective: To assess if TAVI is non-inferior to surgical aortic valve replacement in patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk? N=913 patients. Inclusion criteria: Patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity. TAVI (N=458) VS Surgery (N=455) PRIMARY OUTCOME 4.6 All-cause mortality at 1 year P<.001 for noninferiority 6.6 SECONDARY OUTCOME 7.2 Major bleeding events at 1 year % HR 0.33; 95% CI, 0.24 to 0.45 20.2 10.3 Vascular complications HR, 4.42; 95% CI, 2.54 to 7.71 2.4 14.2 Pacemaker implantation HR, 2.05; 95% CI, 1.43 to 2.94 7.3 Conclusion: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year. JAMA. 2022;327(19):1875-1887. doi:10.1001/jama.2022.5776 M Visualmed

PARADISE MI Trial Summary: Sacubitril-valsartan vs ramipril in acute MI


2021 PARADISE-MI M Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction international, multicenter, randomized, double-blind, active-comparator trial S S 1. Objective: To compare the effects of sacubitril-valsartan and angiotensin converting-enzyme inhibitor, ramipril in patients with acute myocardial infarction 5661 Inclusion criteria: Adults without history of heart failure but spontaneous myocardial infarction with a reduced left ventricular ejection fraction, pulmonary congestion, or both conditions and had 21 of 8 prespecified risk-augmenting factors patients Sacubitril-valsartan group (n=2830) Ramipril group (n=2831) PRIMARY OUTCOME 11.9 Death from any causes % HR 0.88; 95% CI, 0.73 to 1.04; P=1.05 13.2 SECONDARY OUTCOME 7.5 Death from cardiovascular causes or hospitalization for heart failure % HR 0.91; 95% CI, 0.78 to 1.07 8.5 5.9 Death from cardiovascular causes % HR 0.87; 95% CI, 0.71 to 1.08 6.7 12.6 Adverse events % 13.4 Conclusion: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. MA Pfeffer et al. NEJM 2021; 385:1845-1855 Summary by Dr.Shreyash Bhoyar, MBBS M Visualmed