Introduction to Randomized Trials

The SYNTAX score II 2020 (SSII-2020), which was derived and externally validated from randomized trials, was designed to predict death following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel disease and/or left main disease.

Are the results of randomized trials relevant in routine clinical practice?;Medical therapy at discharge in patients admitted for acute coronary syndrome: Data of the French MONICA population registers;Post-infectious myocardial Infarction: Does percutaneous coronary intervention improve outcomes? A propensity-score matched analysis;Prevalence and prognosis of iron deficiency in acute myocardial infarction;Myocardial infarction rates overview during COVID-19 pandemic In France: Results of the MODIF registry;Short-term air pollution concentration variations and ST-elevation myocardial infarction: A case-crossover study from the SCALIM registry;Predictive value of early cardiac mri functional and geometric indexes on adverse left ventricular remodelling in anterior STEMI patients.

BACKGROUND/OBJECTIVE Elderly patients (≥ 80 years) were underrepresented in randomized trials that proved the efficacy and safety of mechanical thrombectomy (MT) in acute ischemic strokes (AIS) due to large vessel occlusion (LVO).

OBJECTIVE Different etiologies of extracranial internal carotid artery steno-occlusive lesions (ECLs) in patients with acute ischemic stroke (AIS) and tandem occlusion (TO) have been pooled together in randomized trials.

Randomized trials with large sample size and excellent quality are necessary before the practical implementation of new techniques.

Large sample size randomized trials are needed to confirm our results.

We continue to recommend the moderately hypofractionated WBI protocols recommended by ASTRO and NCCN and acknowledge their role in standard practice as they are supported by randomized trials with long-term follow-up.

The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data.

8506Background: We published a pooled analysis of 2 randomized trials (STARS/ROSEL) that compared lobectomy with mediastinal lymph node dissection (L-MLND) vs stereotactic ablative radiotherapy (SA.

The curative impact of an extensive lymph node dissection, as currently recommended, remains to be proved, and recently published randomized trials do not provide firm conclusions.

Power calculation for stepped-wedge cluster randomized trials (SW-CRTs) presents unique challenges, beyond those of standard parallel cluster randomized trials, due to the need to consider temporal within cluster correlations and background period effects.

Stepped wedge cluster randomized trials (SW-CRTs) with binary outcomes are increasingly used in prevention and implementation studies.

PURPOSE/OBJECTIVE(S) To conduct the first global individual patient data (IPD) meta-analysis of randomized trials to assess the impact of androgen deprivation therapy (ADT) use and duration with definitive radiotherapy (RT) in localized prostate cancer.

BACKGROUND While multiple randomized trials have evaluated the benefit of radiation therapy (RT) dose escalation and the use and prolongation of androgen deprivation therapy (ADT) in the treatment of prostate cancer, few studies have evaluated the relative benefit of either form of treatment intensification with each other.

Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real-world evidence (RWE) in the evaluation of new treatments or products.

The following questions and topics were raised within the discussion: the importance of additional indicators beyond glycated hemoglobin (HbA1c) for glycemic control assessment in diabetes patients, CGM positioning in International and Russian clinical guidelines, the accuracy of CGM devises and approaches to its assessment, the role of education programs for diabetic patients, including trainings in correct use and data interpretation and analysis of CGM data obtained, clinical evidence analysis for CGM in randomized trials and real world evidence.

Randomized trials have now addressed whether mitral valve repair should be performed concomitantly with coronary artery bypass grafting in the setting of moderate IMR, and whether mitral valve repair or replacement is superior in the setting of severe IMR.

Randomized trials show high long‐term patency for no‐touch saphenous vein grafts in coronary artery bypass grafting.

Background Remdesivir is approved by the US Food and Drug Administration for the treatment of patients hospitalized with coronavirus disease 2019 (COVID-19) and has been shown to shorten time to recovery and improve clinical outcomes in randomized trials.

Anticoagulation therapy in coronavirus disease 2019 (COVID-19) patients still represents matter of debate, and no adequate randomized trials have been published so far fully addressing the topic.

Prospective randomized trials with a larger sample size and longer follow-up are needed for comparison with other techniques of IOL fixation and confirmation of long-term safety profile.

Randomized trials with larger sample size and longer postoperative follow up are suggested for further evaluation of the outcomes and added value.

' Selection criteria We included randomized or non‐randomized trials, controlled before‐after studies, or interrupted time series studies conducted in LMICs (as defined by the World Bank in 2018).

There are defined frameworks and models that outline implementation strategies and assist researchers in identifying barriers and facilitators to achieve implementation and conduct implementation research using methods such as qualitative analysis, parallel group, pre-/postintervention, interrupted time series, and cluster or stepped-wedge randomized trials.

For nearly 30 years, little improvement in the treatment of PTCLs has been noticed due to the paucity of randomized trials and anthracycline-based chemotherapy remains the mainstay of first-line treatment.

Design, Setting, and Participants This post hoc analysis of the phase 2 KEYNOTE-059 (third-line treatment or higher) single-arm trial and the phase 3 KEYNOTE-061 (second-line treatment) and KEYNOTE-062 (first-line treatment) randomized trials included patients with advanced G/GEJ cancer from 52 sites in 16 countries enrolled in KEYNOTE-059, 148 sites in 30 countries enrolled in KEYNOTE-061, and 200 sites in 29 countries enrolled in KEYNOTE-062.

This network meta-analysis of randomized trials evaluates targeted therapies and somatostatin analogues in GEP advanced NETs, either alone or in combination, comparing the efficacy of different single or combined treatment strategies in terms of progression-free survival (PFS).

This review commences with a discussion of the only two existing randomized trials (and a pooled analysis) showing that the addition of RT to immunotherapy improves the abscopal response rate, progression-free survival, and overall survival in metastatic NSCLC patients.

DESIGN The FALCON 1 and 2 studies are Phase 2b, multicenter, double-blind, placebo-controlled, randomized trials to assess safety and efficacy of PGBF treatment in patients who have histologically-confirmed NASH with stage 3 liver fibrosis (FALCON 1; NCT03486899) or compensated cirrhosis (FALCON 2; NCT03486912).

Methods This post-hoc analysis of two double-blind, placebo-controlled, randomized trials (RCTs) investigating the efficacy of GCSB-5 or diacerein as treatments for hand OA analyzed the efficacy of a placebo.

Randomized trials are needed to establish the optimal treatment approach for HNS.

Randomized trials are needed to establish the optimal treatment approach for ASHN.

For accelerated partial breast irradiation, in low-risk breast cancers patients, several phase III randomized trials confirmed that extreme hypofractionation is a valid option.

Several randomized trials have been performed comparing partial breast irradiation (PBI) and whole breast irradiation (WBI) though controversy remains, including regarding differences by PBI technique.

Quality of life data from randomized trials are lacking in older patients with metastatic colorectal cancer (mCRC).

This study is 1 of the most modern large, randomized trials for patients with metastatic colorectal cancer to date and as such represents the standard of care for patients with this disease.

Background: Randomized trials comparing alteplase (ALT) to tenecteplase (TNK) in large vessel occlusion have reported higher rates of recanalization with evidence of better clinical outcomes.

INTRODUCTION The benefits of mechanical thrombectomy in the treatment of patients with acute stroke due to large vessel occlusions (LVOs) have been extensively demonstrated by randomized trials and registries in developed countries.

Evidence review We conducted a meta-analysis of randomized trials comparing the effects of adding iPACK block to ACB versus ACB alone on pain severity at 6 hours postoperatively in adult patients undergoing TKA.

METHODS A systematic review and network meta-analysis of randomized trials of adult patients undergoing total hip or knee arthroplasty were conducted.

In the early 2000’s, several randomized trials failed to show any superiority of PAC use over standard care in different populations, including high-risk surgical patients, general critical care patients, and patients with acute respiratory distress syndrome.

Purpose We sought to examine changes in acute respiratory distress syndrome (ARDS) management over a 12-year period of two successive randomized trials.

OBJECTIVE To conduct a systematic review and network meta-analysis of all randomized trials investigating effect of anti-calcitonin gene related peptide monoclonal antibodies (anti-CGRP mAbs) on disability related to migraine in adult patients.

Recent data from randomized trials with monoclonal antibodies targeting the calcitonin gene related peptide pathway (anti-CGRP mAbs) are controversial, although its role in the pathogenesis of the condition is well documented.

Recent technological advances, together with an increasing body of evidence from randomized trials, have placed coronary computer tomography angiography (CCTA) in the center of the diagnostic workup of patients with coronary artery disease.

With the publication of three large-scale randomized trials (SYNTAX, NOBLE, and EXCEL) the European guidelines were updated in 2018 to recommend PCI as an alternative to CABG in the treatment left main coronary artery disease with a class 1 recommendation in low SYNTAX and a class 2a recommendation intermediate SYNTAX anatomic complexity scores.

As with the current study, most gingerrelated randomized trials seldom meet the criterion of “high quality evidence" because of small sample size and use of unstandardized formulation and evaluation systems.

In the 2020 update to the American Heart Association’s Guidelines for Cardiopulmonary Resuscitation, only 32% of 491 individual recommendations were based on moderate or high quality evidence, and only 11% of the recommendations were based on randomized trials.

Background and purpose Randomized trials confirmed the efficacy and the safety of hypofractionated whole breast irradiation (HF-WBI) in patients with early-stage breast cancer.

e12508Background: Randomized trials in stage 0-II breast cancer have proven that APBI given via HDR implant in 5 days is equivalent to whole breast irradiation (WBI) given in 5-6 weeks in regard to.

Background: Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19).

Background Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19).

Several recent randomized trials suggest that abbreviated dual antiplatelet therapy (DAPT; aspirin plus a platelet P2Y12 receptor antagonist) can.

METHODS We searched PubMed, Embase, Scopus and Cochrane databases to identify randomized trials that investigated the use of dual antiplatelet therapy and vitamin K antagonist and/or Non-vitamin K antagonist oral anticoagulants (NOAC) (triple antithrombotic therapy (TAT)) against single antiplatelet agent and NOAC (dual antithrombotic therapy (DAT)) in the setting of coronary artery disease (CAD) requiring PCI and non-valvular atrial fibrillation.

Methods  Long-term safety of BARI was assessed from 9 completed randomized trials(5 Ph3, 3 Ph2, 1 Ph 1b) and 1 ongoing long-term extension(LTE) study.

Further randomized trials will help in establishing the long-term safety of this novel pacing modality.

This review is limited by the low number of randomized trials and the relatively short follow-up period.

However, the prospective large randomized trials COURAGE, BARI-2D, and ISCHEMIA did not demonstrate a survival benefit of revascularization over medical therapy in stable CAD patients during relatively short follow-up periods.

Study quality was assessed using Cochrane risk of bias tools for randomized trials and the risk-of-bias assessment tool for non-randomized studies (RoBANS) (PROSPERO 2019:CRD42019142409).

The quality of included studies was assessed using the Cochrane risk of bias assessment tool for randomized trials and the modified Newcastle-Ottawa scale for non-controlled trials.

METHOD We meta-analyzed the trial-level hazard ratio and 95% confidence interval of randomized trials that reported the CV outcomes stratified in to three subgroups of normoglycemia, prediabetes and diabetes.

In all five randomized trials, baseline NLR predicted incident CV events and death; the per-quartile increase in risk of MACE was 20% in CANTOS [95% confidence interval (CI) 14-25%, P < 0.

Renal artery stenosis may be treated by revascularization using either percutaneous (balloon angioplasty with or without stenting) or less commonly open surgical procedures, both with excellent primary patency rates of over 90%; however, randomized trials of catheter-based interventions have failed to demonstrate a longer term benefit with respect to blood pressure control and renal function as well as improved overall survival over optimal medicinal management alone.

Whilst data from phase 2 randomized trials suggesting an improved overall survival (OS) with this treatment is promising, it has also illustrated the heterogeneity in this patient population and treatment.

Objective Despite growing expertise and wide application of venovenous extracorporeal membrane oxygenation (VV ECMO) treatment for acute respiratory distress syndrome (ARDS) of different origin and during pandemics (H1N1 Influenza A virus and SARS-CoV-2), large reports are few and pertain mostly to multicenter registries, and randomized trials are difficult to perform.

Objective Despite growing expertise and wide application of venovenous extracorporeal membrane oxygenation (VV ECMO) treatment for acute respiratory distress syndrome (ARDS) of different origin and during pandemics (H1N1 Influenza A virus and SARS-CoV2), large reports are few and pertain mostly to multicentre registries, while randomized trials are difficult to perform.

Nonetheless, progress has been limited by a number of factors such as the low number of controlled randomized trials, small sample sizes, variety of stimulation parameters precluding comparability and incomplete or questionable sham-conditions.

Although the researchers define limitations of their study, such as the small sample size and non-blinded design, they conclude that compared with fluoroquinolone alone, dual therapy with EcN and levofloxacin “seems to favor better control of symptoms and reduce the risk of biological recurrences”, although larger randomized trials are needed to confirm the results.

12112 Background: Previous randomized trials in cancer patients suggest that DOACs are non-inferior to LMWHs for preventing recurrent venous thromboembolism (VTE).

Randomized trials have reported that aspirin reduces the risk of recurrent venous thromboembolism, but the clinical relevance remains limited, because direct oral anticoagulants are more effective.

Transcarotid artery revascularization (TCAR) with a flow reversal neuroprotection system was designed to reduce the embolic risk associated with the transfemoral approach, but randomized trials have yet to be published comparing transfemoral carotid artery stenting with TCAR.

Introduction: Previous analyses of randomized trials comparing carotid artery stenting (CAS) versus carotid endarterectomy (CEA) have revealed varying sex-associated risk.

IMPORTANCE Several randomized trials of neoadjuvant chemo-immunotherapy in early triple negative breast cancer (TNBC) have been recently reported, showing conflicting results.

For older patients with clinically lymph node-negative breast cancer who have estrogen receptor-positive tumors and are treated with tamoxifen, randomized trials comparing axillary lymph node dissection (ALND) versus no ALND show that the omission of ALND improves patient quality of life and has no adverse effects on mortality.

Beyond the overall relapse-free survival (RFS) advantage demonstrated in randomized trials (RCT) of adjuvant anti-PD-1 immunotherapy in radically resected stage III-IV melanoma, key issues about subgroups of interest have been raised in recent years, with non-conclusive results when considering single studies.

In the realm of postallo-HCT maintenance therapy, the FLT3 inhibitor sorafenib has yielded superior results in terms of OS and relapse-free survival in randomized trials compared with observation.

PURPOSE/OBJECTIVE(S) Multiple randomized trials incorporating locally ablative therapy in oligometastatic non-small cell lung cancer (NSCLC) have used number of metastatic sites to identify which patient populations benefit from aggressive local therapy.

Support for oligometastatic non-small cell lung cancer (NSCLC) has since been provided by multiple retrospective studies and then prospective randomized trials demonstrating better survival in this patient population after aggressive consolidative treatment.

Acalabrutinib was evaluated in two phase 3 multicenter randomized trials.

Here we describe detailed results on hematologic efficacy in two phase 3, randomized trials (the PRO2TECT trials) in adult patients with non–dialysis-dependent (NDD) CKD and anemia, in which vadadustat met prespecified noninferiority criteria compared to darbepoetin alfa, with respect to hematologic efficacy (correction/maintenance of hemoglobin [Hb] target concentrations).

BACKGROUND Recent randomized trials including low-risk patients showed positive results for transcatheter aortic valve replacement (TAVR) compared to surgical aortic valve replacement (SAVR), but patients with non-tricuspid aortic valve (NTAV), severe coronary artery disease (SevCAD), and those requiring concomitant mitral/tricuspid valve (CMTV) or concomitant ascending aorta replacement (CAAR) interventions were excluded.

Because of the potential for selection bias and absence of a control group treated surgically for bicuspid aortic stenosis, randomized trials are needed to adequately assess the efficacy and safety of transcatheter aortic valve replacement for bicuspid aortic stenosis in patients at low surgical risk.

Again, more research, preferably large randomized trials, is required to compare the long-term clinical efficacy of NOM with appendicectomy.

BACKGROUND Randomized trials evaluating the Orsiro biodegradable polymer sirolimus-eluting stent (BP-SES; 60 and 80 μm strut thickness for stent diameters ≤3 and >3 mm, respectively) did not stratify according to vessel size and failed to specify the impact of ultrathin-strut thickness on long-term clinical outcomes compared with durable polymer everolimus-eluting stents (DP-EES).

Background: High flow nasal cannula (HFNC) therapy for bronchiolitis has become increasingly popular,however early initiation did not impact patient outcomes in the two randomized trials and is reported to be15x more costly than standard low flow nasal cannula (LFNC) We hypothesized that lack of initiation criteriafor use of HFNC was resulting in overutilization Objective: We sought to increase trials of LFNC in acute viralbronchiolitis in order to decrease the use of HFNC Our primary aim is to increase the percent of LFNCutilization prior to HFNC initiation by 50% by April 2020 Design/Methods: We undertook a multidisciplinaryquality improvement project involving Hospital Medicine, Emergency Medicine and Critical Care physicians,along with respiratory therapy and nursing We revised our existing bronchiolitis protocol to include LFNCfailure defined as no improvement in oxygen saturation, heart rate or respiratory rate within 30-60 minutes ofinitiation and protocolized LFNC treatment failure to precede HFNC initiation Our pathway change took effectDecember 1st, 2019 Inclusion criteria were: &lt; 2 years admitted to PHM with a primary diagnosis of any ICD-10 code for bronchiolitis PICU transfer rates serve as the balancing measure and statistical process controlgrouping data in two-week increments is the primary method of analysis Results: Baseline data for the seasonpreceding our intervention (2018-2019) revealed HFNC usage in floor patients with bronchiolitis to be 62%(61/98), with 39% (24/61) undergoing a trial of LFNC prior to initiation of HFNC Post-intervention datademonstrate an increase in LFNC trials to 73% (29/40) and a concomitant decrease in HFNC utilization to 48%(40/84) (Figure 1 a/b) Rules for special cause were satisfied for the LFNC measure (2 out 3 consecutivemeasures above 2 sigma) but not for the HFNC measure when the project had to be stopped due to the SARS-CoV2 epidemic which was an external pressure against the use of HFNC (an aerosolizing procedure) Ourbalancing measure appears stable with a pre-intervention PICU transfer rate of 6 1% (n=98) and a post-intervention rate of 2 9% (n=68) Conclusion: Preliminary data suggests a simple intervention consisting ofestablishing LFNC treatment failure criteria in patients with moderate bronchiolitis may reduce HFNC usewithout adverse effects.

The study is a secondary analysis of randomized trials in immunocompromised patients, including all patients who received high-flow nasal cannula (HFNC).

PURPOSE/OBJECTIVE(S) Randomized trials have shown improved local control (LC) but no overall survival (OS) benefit with the addition of non-ablative radiation therapy (RT) dose compared to chemotherapy (CT) alone for pancreas cancer (PCa).

Purpose Phase 2 randomized trials suggest that stereotactic ablative radiation therapy improves progression-free and overall survival in patients with oligometastatic cancer, with phase 3 trials currently testing stereotactic ablative radiation therapy in up to 10 metastases.

Longitudinal cluster randomized trial (LCRT) and crossover cluster randomized trial (CCRT) are two variants of cluster randomized trials.

Results Ninety-one studies, including 4729 women, met inclusion criteria (6 randomized trials, 1 cluster randomized trial, 15 nonrandomized studies, and 69 case series).

Therefore, to achieve sufficient power to answer this question, we performed a meta-analysis of randomized trials evaluating the benefit of RT dose escalation in localized prostate cancer.

OBJECTIVE Several prospective randomized trials have shown that hypofractionation has the same efficacy and safety as the conventional fractionation in the treatment of localized prostate cancer.

MATERIALS/METHODS We searched PubMed, EMBASE, CENTRAL for randomized trials comparing two or more adjuvant breast RT treatment approaches for patients with early-stage breast cancer treated with breast conservation surgery.

PURPOSE/OBJECTIVE(S) Randomized trials in selected early-stage breast cancer patients with up to 10-year follow-up have proven that Accelerated Partial Breast Irradiation (APBI) given via High Dose Rate (HDR) implant bid in 5 days is equivalent to whole breast irradiation (WBI) given q.

Methods We performed a meta-analysis of randomized trials that compared ICI plus RT with placebo plus RT or ICI alone for the treatment of advanced nonsmall-cell lung cancer (NSCLC) and prostate cancer.

The Choosing Wisely recommendation to omit sentinel lymph node biopsy in women over the age of seventy with early stage, clinically node-negative, hormone-positive, HER2-negative invasive breast cancer was based on the results of multiple prospective randomized trials demonstrating that survival in this target population is independent of nodal tumor burden.

We consider five asymptotically unbiased estimators of intervention effects on event rates in non-matched and matched-pair cluster randomized trials, including ratio of mean counts r 1 , ratio of mean cluster-level event rates r 2 , ratio of event rates r 3 , double ratio of counts r 4 , and double ratio of event rates r 5.