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

PARADISE MI Trial: Is Sacubitril/valsartan (Entresto) useful in patients with acute MI?

The PARADISE MI trial is the first of the 10 new trials visual abstracts that we have added to the app. You can download the JPEG of the visual abstract from below. You can use it any way you like as long as you cite the visualmed app or the website along with the original article.

PARADISE MI Trial Entresto in acute MI

Use of Sacubitril/valsartan in Acute MI?

Sacubitril, a neprilysin inhibitor, has shown to be beneficial when combined with an ARB in patients with chronic heart failure. A similar hypothesis was generated that it might be useful in patients with acute ischemic HF or patients with acute MI who had reduced EF or clinical heart failure. To prove this hypothesis, the PARADISE MI trial was designed. The recruitment was intense and the authors were able to recruit more than 5,000 patients that suitably powered this prospective superiority trial.

Inclusion criteria included patients with reduced EF after the MI

The included population was diverse and consisted of 24% females. Only those acute MI patients were included whose Left ventricular ejection fraction (LVEF) was ≤40% with or without pulmonary congestion. This is important as neprilysin inhibition has been primarily found to be useful in heart failure patients. Also, recall that the PIONEER-HF trial showed significant improvement of NT-proBNP of patients with acute HF who were put on neprilysin inhibition.

PIONEER HF Trial entresto in acute heart failure

Sacubitril/valsartan failed to show superiority over ACEi Ramipril

The primary outcome of cardiovascular (CV) death, first HF hospitalization, or outpatient HF occurred in 11.9% sacubitril/valsartan patients vs. 13.2% in the ramipril group. (p = 0.17) The findings are significantly different from prior trials. One key difference is the use of Ramipril and acute MI population who had MI within the prior 7 days. In the prior studies, the comparison was made with enalapril such as seen in the PARADIGM-HF trial which was done for chronic heart failure patients.

PARADIGM HF Trial ARNI in heart failure

Incremental benefit and safety in acute MI

The authors of PARADISE-MI argued that there is an incremental benefit of ARNI in this specific patient group but is that enough to compel cardiologists to prescribe this drug? ACEi and ARBs are cheaper and easily accessible and with newer data physicians are leaning more towards prescribing these meds over ARNI especially in the vulnerable population who are unable to afford their meds.

How to keep yourself updated with the latest medical literature using the Visualmed app

Did you know that there are around 30,000 journals that are publishing more than 2 million articles each year? (source). The amount of data inflow is exponential and the most difficult task is to keep yourself up to date with all this information. If you’re a physician, the only time you’ll be able to read any scientific article is either during a journal club meeting or maybe on weekends if you don’t have any family. The truth is we are publishing way more than we can digest. If we talk about just cardiology, ~ 87 landmark, practice-changing trials were published in 2020 (source). Most of these trials get traction through medical media websites but some of the important ones are simply missed and get archived without getting much traction. Now the question remains, how do we keep ourselves up to date with all this knowledge?

In 2018, I was a medicine resident at the University of Connecticut Health Center in Farmington CT, USA. I was scheduled to rotate through the ICU during the latter half of the year. During that rotation, two important clinical trials were published, namely the SALT-ED and the SMART trial. These trials highlighted an important question in clinical medicine which is whether to use balanced crystalloids or just saline in hospitalized and critically ill patients respectively. As a senior ICU resident, it was difficult for me at that time to go through the complete study so I came up with an idea to summarize the key points of the trial as a visual infographic. The SALT-ED trial was the first study that I visualized. My colleagues loved the infographic summary and asked if I could summarize other important studies as well. This was how Visualmed started. The idea started with a website, where I compiled all the key trials but keeping up with even landmark studies was difficult. Eventually, I decided to focus on app format only as it was easier to manage compared to the website. Now, after 3 years of hard work, I have finally launched the free version of the app that contains ~1000 summaries of landmark clinical trials.

When designing the app, my idea was to keep it as simple as possible. This is the reason the landing page of Visualmed is simply a list of medical topics and subcategories with a search bar on top. The search function is dynamic. This means if you start typing a drug or a disease name, the trials on that particular topic will pop up in real-time provided that it’s available in the app. Unlike other apps in the same category, Visualmed contains a one-page summary only. This means that once you tap on a trial, it’ll pop up one verticle image that squeezes all the key information from that trial.

I try to focus on the primary outcome and 2 key secondary outcomes of the study. One important part that I’m trying to introduce is the key limitation of the trial. The plan is to update all the available infographics and add key limitations to each of those. The idea of Visualmed is to provide a key concept of the trial. This is in no way an alternative to reading and going through the full study. Nevertheless, we do need a platform or a search engine for practice-changing evidence-based medicine and Visualmed provides just that.

The app has now more than 30,000 physicians who used it on daily basis for quick reference of the studies. Each trial is linked to its original study and I believe this provides a unique source to encourage physicians to go through these studies and improve their own knowledge as well as practice evidence-based medicine. The app is currently in its initial stages. I have shortlisted more than 5,000 landmark studies that had been published in notable journals such as NEJM, JAMA, BMJ and the Lancet. The plan is to add all those studies to the app eventually. Right now, the app gets updated with 40 new trials every month and we are trying to increase that to at least 50-70 trials a month.

In conclusion, if you read through this article, I would like to encourage you to download the app. It’s totally free and there are no advertisements. The app is meant to be used by physicians and healthcare workers only. Here are the download links:

Visualmed for iPhone

Visualmed for Android