Abstract W P113: Prolonged Use of Clopidogrel and Aspirin and Stroke Risk in Intracranial Stenosis in SAMMPRIS

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Christine Holmstedt ◽  
Michael J Lynn ◽  
Tanya N Turan ◽  
Colin P Derdeyn ◽  
David Fiorella ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Statistical Power ◽  
Intracranial Stenosis ◽  
Antithrombotic Agent ◽  
Logrank Test ◽  
Major Hemorrhage ◽  
Exact Test ◽  
Lipid Disorder ◽  
Primary Endpoints ◽  
Event Rates

Background: In the SAMMPRIS trial, the use of combination aspirin and clopidogrel for 90 days after enrollment could be one reason that the outcome of patients in the medical arm was better than expected. The SAMMPRIS protocol required stopping clopidogrel after 90 days unless the patient had a non-neurological indication for continued use. We sought to compare outcomes in patients on vs. off clopidogrel beyond 90 days. Methods: For patients who did not have a primary endpoint within 90 days after enrollment (n = 397), we compared baseline features (t and Fisher’s exact tests), survival curves for the primary endpoint beyond 90 days after enrollment (the logrank test), and major hemorrhages (Fisher’s exact test) in patients on vs. off clopidogrel in the medical arm and stenting arms. Results: In the medical and stenting groups combined, baseline factors that were significantly (p<0.05) different between those on vs. off clopidogrel beyond 90 days (all higher in on clopidogrel group) were: age, diabetes, lipid disorder, coronary disease, SBP, and on antithrombotic agent at qualifying event. The table shows the primary endpoints and major hemorrhages in patients on vs. off clopidogrel in both treatment groups. Conclusion: This analysis, which was underpowered to detect even very large differences in event rates, suggests that prolonged use of clopidogrel plus aspirin may lower the risk of stroke in medically treated patients with intracranial stenosis, but increase the risk of major hemorrhage. Further studies with higher statistical power are needed to test this hypothesis.

Abstract 81: Recurrent Stroke Risk After Angioplasty and Stenting for Symptomatic Intracranial Stenosis: Data From the SAMMPRIS Trial

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Colin Derdeyn ◽  
David Fiorella ◽  
Tanya Turan ◽  
Jean Montgomery ◽  
Bethany Lane ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Primary Endpoint ◽  
Imaging Modality ◽  
Recurrent Stroke ◽  
Intracranial Stenosis ◽  
Stent Restenosis ◽  
Primary Endpoints ◽  
Angioplasty And Stenting ◽  
In Stent Restenosis

Purpose: To investigate the incidence and clinical characteristics of recurrent stroke beyond 30 days after uncomplicated angioplasty and stenting for symptomatic intracranial stenosis. Methods: Primary endpoints in SAMMPRIS (Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke) after 30 days past enrollment were defined as ischemic stroke in the territory or any stroke or death within 30 days of a subsequent revascularization procedure. Endpoints were independently and blindly adjudicated. Study records and imaging studies of subjects randomized to the stent arm with post-30 day primary endpoints were reviewed. Instent restenosis (ISR) was categorized as severe (>70%), moderate (50-69%) or mild (< 50%) based on consensus of two reviewers. Findings were categorized as definite, probable, or indeterminate based on imaging modality and study quality. Results: 224 subjects were randomized to the stent arm and 33 suffered a primary endpoint within 30 days of enrollment. Nineteen of the remaining 191 subjects (9.9%) suffered a primary endpoint during follow up (median follow up of 32.4 months). Eighteen had an ischemic stroke in the territory and one had a symptomatic intracranial hemorrhage after repeat angioplasty for in stent restenosis (ISR). In the 18 patients with ischemic stroke, the vascular imaging findings were: complete stent occlusion in 2 (1 of these was acutely revascularized and severe underlying ISR was identified), severe ISR by catheter angiography in 5, severe ISR or occlusion by computed tomographic angiography (CTA) in 1, probable ISR by CTA or magnetic resonance angiography (MRA) in 3, moderate stenosis on angiography in 2 (1 with ISR and 1 with a residual stenosis), indeterminate in 2, normal in 2, and not done in 1. Lesion locations included: distal internal carotid (6), petrous carotid (1), basilar (5), middle cerebral (6), and vertebral (1) arteries. Median time to recurrent stroke was 7.7 months from enrollment (2.2 to 28.2 months). Conclusions: The incidence of recurrent stroke beyond 30 days after uncomplicated angioplasty and stenting in the SAMMPRIS trial was nearly 10% over a mean follow-up of almost 3 years. In stent restenosis was associated with the majority of recurrent strokes.

Roxadustat for anemia in patients with end-stage renal disease incident to dialysis

2021 ◽  
Author(s):  
Robert Provenzano ◽  
Evgeny Shutov ◽  
Liubov Eremeeva ◽  
Svitlana Korneyeva ◽  
Lona Poole ◽  
...  
Keyword(s):  
Rescue Therapy ◽  
Controlled Trial ◽  
Epoetin Alfa ◽  
Open Label ◽  
Treatment Groups ◽  
Intention To Treat ◽  
Primary Endpoints ◽  
Stage Renal Disease ◽  
End Stage ◽  
Event Rates

Abstract Background We evaluated the efficacy and safety of roxadustat vs. epoetin alfa for the treatment of chronic kidney disease (CKD) related anemia in patients new to dialysis. Methods This was a phase 3, open-label, epoetin alfa-controlled trial. Eligible adults were on hemodialysis/peritoneal dialysis for ≥2 weeks and ≤4 months before randomization and had mean hemoglobin ≤10.0 g/dL. Primary endpoints were mean hemoglobin (g/dL) change from baseline averaged over weeks 28–52 regardless of rescue therapy (non-inferiority criterion: lower limit of 95% CI for treatment difference &gt; −0.75) and percentage of patients achieving a hemoglobin response between weeks 1–24 censored for rescue therapy (non-inferiority margin for between-group difference: −15%). Adverse events were monitored. Results The intention-to-treat population included patients randomized to roxadustat (n = 522) or epoetin alfa (n = 521). Mean (SD) hemoglobin changes from baseline averaged over weeks 28–52 were 2.57 (1.27) and 2.36 (1.21) in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior (least-squares mean difference: 0.18 [95% CI: 0.08, 0.29]) to epoetin alfa. Percentages of patients with a hemoglobin response were 88.2% and 84.4% in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior to epoetin alfa (treatment-group difference: 3.5% [95% CI: −0.7%, 7.7%]). Adverse event rates were comparable between treatment groups. Conclusions Roxadustat was efficacious for correcting and maintaining hemoglobin levels compared to epoetin alfa. Roxadustat had an acceptable safety profile.

scholarly journals Association of P10L Polymorphism in Melanopsin Gene with Chronic Insomnia in Mexicans

2021 ◽  
Vol 18 (2) ◽  
pp. 571
Author(s):  
Bianca Ethel Gutiérrez-Amavizca ◽  
Ernesto Prado Montes de Oca ◽  
Jaime Paul Gutiérrez-Amavizca ◽  
Oscar David Castro ◽  
Cesar Heriberto Ruíz-Marquez ◽  
...  
Keyword(s):  
Statistical Power ◽  
Medical Condition ◽  
Severity Index ◽  
Recessive Model ◽  
Chronic Insomnia ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Increased Risk ◽  
Fisher’S Exact Test ◽  
And Function

The aim of this pilot study was to determine the association of the P10L (rs2675703) polymorphism of the OPN4 gene with chronic insomnia in uncertain etiology in a Mexican population. A case control study was performed including 98 healthy subjects and 29 individuals with chronic insomnia not related to mental disorders, medical condition, medication or substance abuse. Samples were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genetic analyses showed that the T allele of P10L increased risk to chronic insomnia in a dominant model (p = 1 ×10−4; odds ratio (OR) = 9.37, CI = 8.18–335.66, Kelsey statistical power (KSP) = 99.9%), and in a recessive model (p = 7.5 × 10−5, OR = 9.37, KSP = 99.3%, CI = 2.7–34.29). In the insomnia group, we did not find a correlation between genotypes and chronotype (p = 0.219 Fisher’s exact test), severity of chronic insomnia using ISI score (p = 0.082 Fisher’s exact test) and ESS score (p ˃ 0.999 Fisher’s exact test). However, evening chronotype was correlated to daytime sleepiness severity, individuals with an eveningness chronotype had more severe drowsiness according to their insomnia severity index (ISI) score (p = 0.021 Fisher’s exact test) and Epworth sleepiness scale (ESS) score (p = 0.015 Fisher’s exact test) than the morningness and intermediate chronotype. We demonstrated that the T allele of the P10L polymorphism in the OPN4 gene is associated with chronic insomnia in Mexicans. We suggest the need to conduct larger studies in different ethnic populations to test the probable association and function of P10L and other SNPs in the OPN4 gene and in the onset of chronic insomnia.

Abstract 15116: The Prognostic Value of Left Ventricular Mechanical Dyssynchrony in Patients With Idiopathic Dilated Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yangjie Li ◽  
Yuanwei Xu ◽  
Siqi Tang ◽  
Xiaoyue Zhou ◽  
Yucheng Chen
Keyword(s):  
Dilated Cardiomyopathy ◽  
Primary Endpoint ◽  
Prognostic Value ◽  
Mechanical Dyssynchrony ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Ratio Estimate ◽  
Apical Level ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Cmr Imaging

Backgrounds: The mechanical dyssynchrony has been commonly observed in idiopathic dilated cardiomyopathy (DCM) patients, and several cardiac magnetic resonance (CMR) imaging techniques were used to evaluate the mechanical dyssynchrony. Standard deviation of time-to-peak (T2Psd) and uniformity ratio estimate (URE) indices are two widely used parameters to reflect the incoordinate movement of the left ventricle. However, the prognostic value of mechanical dyssynchrony in DCM patients is not clear. Methods and Results: We prospectively enrolled 402 DCM patients undergoing CMR imaging between Jun 2012 to Sep 2018. Mechanical dyssynchrony was measured as T2Psd and URE indices by CMR deformable registration algorithm (DRA) analysis. The primary endpoint was defined as all-cause mortality and heart transplantation, and the secondary endpoint was a combination of primary endpoint, aborted sudden cardiac death, and heart failure readmission. Univariate and multivariate Cox regression analyses were performed to identify the association between variables and outcome. Survival curves were obtained by Kaplan-Meier survival analysis and compared by log-rank test. During a median follow-up of 25.1 months (IQR: 16.2-41.6), there were 57 patients reached primary endpoints, and secondary endpoints occurred in 132 patients. Circumferential uniformity ratio estimate (CURE) at basal, mid and apical level, radial uniformity ratio estimate (RURE)at mid and apical level and longitudinal uniformity ratio estimate (LURE) were significantly worse in patients with primary endpoint compared to patients without primary endpoint. While no significant differences were observed regarding the T2Psd value between patients with and without primary endpoints. In multivariate analysis, CURE at apical level was independently associated with primary endpoints (HR 0.214, P=0.005) and secondary endpoints (HR 0.402, P=0.018). Furthermore, among patients with LVEF <35% or presence of LGE, those with decreased CURE at apical level (<0.917) showed a significantly higher rate of adverse outcome. Conclusion: The CURE at apical level is an independent predictor of adverse cardiac events in DCM patients. Compared with T2Psd, URE index is a better predictor of adverse events.

Parenteral Iron Therapy: A Single Institution's Experience Over a 5-Year Period

2005 ◽  
Vol 3 (6) ◽  
pp. 791-795 ◽  
Author(s):  
Christopher A. Laman ◽  
Scott B. Silverstein ◽  
George M. Rodgers
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Iron Sucrose ◽  
Iron Therapy ◽  
Iron Dextran ◽  
Serious Adverse Events ◽  
Exact Test ◽  
Parenteral Iron ◽  
Parenteral Iron Therapy ◽  
Event Rates

Many patients require parenteral iron therapy for optimal correction of anemia, including cancer patients who require erythropoietic drugs. Available parenteral iron therapy options include iron dextran, iron gluconate, and iron sucrose. The purpose of this study is to summarize our institution's experience with parenteral iron therapy over a 5-year period, with a focus on comparative safety profiles. All patients receiving parenteral iron therapy over this period were included in the analysis. Chi-squared test and Fisher's exact test were used to compare the adverse event rates of each product. A total of 121 patients received 444 infusions of parenteral iron over this period. Iron dextran was the most commonly used product (85 patients) and iron sucrose was the least used (2 patients). Iron gluconate was used by 34 patients. Overall adverse event rates per patient with iron dextran and iron gluconate were 16.5% and 5.8%, respectively (P = .024). Premedication with diphenhydramine and acetaminophen before infusions of iron dextran reduced adverse event rates per infusion from 12.3% to 4.4% (P = .054). Test doses of iron dextran were used 88% of the time for initial infusions of iron dextran. All adverse events for all parenteral iron products were mild or moderate. There were no serious adverse events and no anaphylaxis was observed. Our results suggest that, if test doses and premedications are used, iron dextran is an acceptable product to treat iron deficiency.

Three-year results of phase I retinal gene therapy trial for CNGA3-mutated achromatopsia: results of a non randomised controlled trial

2021 ◽  
pp. bjophthalmol-2021-319067
Author(s):  
Felix Friedrich Reichel ◽  
Stylianos Michalakis ◽  
Barbara Wilhelm ◽  
Ditta Zobor ◽  
Regine Muehlfriedel ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Primary Endpoint ◽  
Statistical Power ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Small Sample ◽  
Functional Improvement ◽  
Limiting Factor ◽  
Serious Adverse Events

AimsTo determine long-term safety and efficacy outcomes of a subretinal gene therapy for CNGA3-associated achromatopsia. We present data from an open-label, nonrandomised controlled trial (NCT02610582).MethodsDetails of the study design have been previously described. Briefly, nine patients were treated in three escalating dose groups with subretinal AAV8.CNGA3 gene therapy between November 2015 and October 2016. After the first year, patients were seen on a yearly basis. Safety assessment constituted the primary endpoint. On a secondary level, multiple functional tests were carried out to determine efficacy of the therapy.ResultsNo adverse or serious adverse events deemed related to the study drug occurred after year 1. Safety of the therapy, as the primary endpoint of this trial, can, therefore, be confirmed. The functional benefits that were noted in the treated eye at year 1 were persistent throughout the following visits at years 2 and 3. While functional improvement in the treated eye reached statistical significance for some secondary endpoints, for most endpoints, this was not the case when the treated eye was compared with the untreated fellow eye.ConclusionThe results demonstrate a very good safety profile of the therapy even at the highest dose administered. The small sample size limits the statistical power of efficacy analyses. However, trial results inform on the most promising design and endpoints for future clinical trials. Such trials have to determine whether treatment of younger patients results in greater functional gains by avoiding amblyopia as a potential limiting factor.

Abstract 6: Interim Report of the Weave Trial: First 102 Consecutive on Label Patients

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Michael J Alexander ◽  
John C Chaloupka ◽  
Alois Zauner ◽  
Blaise Baxter ◽  
Richard Callison ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Best Practice ◽  
Therapy Resistance ◽  
Resistance Testing ◽  
P Value ◽  
Primary Analysis ◽  
Exact Test ◽  
Off Label ◽  
Analysis Group ◽  
Intracranial Atherosclerotic Disease

Purpose: The initial FDA approval trial of the self-expanding Wingspan stent for symptomatic intracranial atherosclerotic disease demonstrated a 4.5% periprocedural complication rate. Subsequently, similar on-label registry data was reported. The WEAVE Trial is a prospective, consecutive enrollment, single-arm, post-market surveillance trial evaluating periprocedural outcomes in patients with the revised FDA indications for use. Methods: Data for the first 102 on-label patients for which completed data is available are included in this report. The primary analysis endpoints included periprocedural stroke, death, or symptomatic bleed within 72 hours of the stenting procedure in patients who were treated on label. A subgroup of the participating sites included anti-platelet therapy resistance testing and correction, if needed, in their treatment of the patient. All patient outcomes were separately adjudicated by a stroke Neurologist by 72 to 96 hours post procedure. Results: In the initial 122 consecutive patients enrolled with completed data, 102 patients were treated on label and are included in the primary analysis, and 20 patients were treated off label and were part of secondary analyses. The mean stenosis in the primary analysis group was 83% with target artery break down as follows: 40.2% MCA, 25.5% ICA, 19.6% Basilar, 14.7% Vertebral or VB junction. Of the 102 patients in the primary analysis, 3 patients (2.9%) reached a primary endpoint of stroke, symptomatic bleed, or death within 72 hours. In the off label group, 4 of the 20 patients (20%) reached a primary endpoint within that period. Conclusions: The early interim analysis of the first 102 patients of WEAVE trial has demonstrated a very low periprocedural morbidity and mortality of 2.9%. This is lower than the high periprocedural event rate in the SAMMPRIS trial, and statistically better than the outcomes in the off label group (Fisher’s Exact test p value 0.014). This early data provides impetus to continue to collect data in this trial, and lends support to the concept that refined patient selection criteria and establishment of best practice techniques and management for these patients can substantially decrease the peri-procedural risk of intracranial stenting.

Abstract T MP35: Frequency, Risk Factors, and Impact of Coexistent Small Vessel Disease in the SAMMPRIS Trial

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Hyung-Min Kwon ◽  
Michael J Lynn ◽  
Tanya N Turan ◽  
Colin P Derdeyn ◽  
David Fiorella ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Stroke Recurrence ◽  
Logrank Test ◽  
Exact Test ◽  
Vessel Disease ◽  
Atherosclerotic Stenosis ◽  
The Impact

Background: Intracranial atherosclerotic stenosis (ICAS) and small vessel disease (SVD) may coexist. We investigated the frequency and risk factors for SVD in SAMMPRIS patients and the impact of SVD on stroke recurrence in the medical arm of the trial. Methods: Of 451 patients enrolled in SAMMPRIS, 313 had baseline brain MRIs read centrally for SVD. SVD was defined by any of the following: old lacunar infarction, Fazekas score of 2-3 for white matter hyperintensities, or microbleeds. We compared risk factors in patients with vs. without SVD using Fisher’s exact test (for percentages), independent groups t test (for means) or Wilcoxon rank sum test (for medians), and compared the survival curves of patients with vs. without SVD in the medical arm for ischemic stroke in the territory of the stenotic artery and any ischemic stroke using the logrank test. Results: Of the 313 patients, 161 (51.4%) had SVD on the baseline MRI. Variables that were significantly (p<0.05) higher in patients with SVD were age, diabetes, lipid disorder, baseline SBP, coronary disease, and old infarct in the territory. The Kaplan-Meier curves in the figure show that patients with SVD were at significantly higher risk of any ischemic stroke (p = 0.048) but not stroke in the territory (p = 0.10) compared with patients without SVD. Conclusion: SVD in patients with ICAS is common, especially in patients who are older, diabetic, hyperlipidemic, and have higher SBP. Patients with ICAS and coexistent SVD are at higher risk of any ischemic stroke but may not be at higher risk for stroke in the territory.

Encephaloduroarteriosynangiosis (EDAS) revascularization for symptomatic intracranial atherosclerotic steno-occlusive (ERSIAS) Phase-II objective performance criterion trial

2020 ◽  
pp. 174749302096725
Author(s):  
Nestor R Gonzalez ◽  
Hao Jiang ◽  
Patrick Lyden ◽  
Shlee Song ◽  
Konrad Schlick ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Medical Management ◽  
Performance Criterion ◽  
Atherosclerotic Disease ◽  
Intracranial Atherosclerotic Disease ◽  
Objective Performance ◽  
Endpoint Event ◽  
One Year ◽  
Event Rates

Background Intracranial atherosclerotic disease (ICAD) is one of the most challenging stroke etiologies, with frequent recurrences despite optimized medical management. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization method that produces extra-cranial collaterals to intracranial vessels. We present the results of a phase-II trial of EDAS in intracranial atherosclerotic disease patients. Aims To evaluate the feasibility, safety, and preliminary efficacy of EDAS in intracranial atherosclerotic disease patients. Methods ERSIAS was a prospective objective-performance-criterion trial of EDAS plus intensive medical management (IMM) in intracranial atherosclerotic disease (ICAD) patients failing medical treatment. Primary endpoint was any stroke/death within 30-days post-surgery or stroke in the territory of the qualifying artery beyond 30 days. The primary analysis compared event rates through one year with an objective-performance-criterion based on a 10% reduction from the 20% rate in the intensive medical management arm of the stenting versus aggressive medical management for preventing recurrent stroke in intracranial stenosis trial (SAMMPRIS) in patients with poor collaterals. Event rates through two years were compared with propensity-score-matched (PSM) medically treated patients from SAMMPRIS and the carotid occlusion surgery study (COSS). Results During a median follow-up of 24.5 months, 5 (9.6%) of 52 patients had a primary endpoint event. The primary endpoint rate at one year met the threshold for nonfutility and advancement to phase III (<10%). In the sensitivity analysis, primary endpoint event rate at two years was lower than in PSM controls, 9.6% versus 21.2% (p < 0.07). Overall, 86% of EDAS-plus-intensive medical management patients were functionally independent at last follow-up and 89% demonstrated neovascularization. There were two (3.8%) surgical complications and no intracranial hemorrhages. Conclusion ERSIAS phase II provides evidence of safety and strong signals of efficacy of EDAS-plus-intensive medical management, supporting advancement to a seamless phase-IIb/III trial. Clinical Trial Registration URL: https://www.clinicaltrials.gov.NCT01819597 .

scholarly journals Non-inferiority trials using a surrogate marker as the primary endpoint: An increasing phenotype in cardiovascular trials

2020 ◽  
Vol 17 (6) ◽  
pp. 723-728
Author(s):  
Behnood Bikdeli ◽  
César Caraballo ◽  
John Welsh ◽  
Joseph S Ross ◽  
Sanjay Kaul ◽  
...  
Keyword(s):  
England Journal ◽  
Clinical Outcome ◽  
New England ◽  
Clinical Outcomes ◽  
Primary Endpoint ◽  
European Heart Journal ◽  
Surrogate Marker ◽  
Surrogate Markers ◽  
Primary Endpoints ◽  
Number Of Patients

Background/aims Non-inferiority trials are increasing in cardiovascular medicine, with approval of many drugs and devices on the basis of such studies. Surrogate markers as primary endpoints have been also more frequently used for efficient assessment of cardiovascular interventions. However, there is uncertainty about their concordance with clinical outcomes. Non-inferiority design using a surrogate marker as a primary endpoint may pose particular challenges in clinical interpretation. We sought to explore the publication trends, methodology, and reporting features of non-inferiority cardiovascular trials that used a primary surrogate marker as the primary endpoint. Methods We searched six high-impact journals ( The New England Journal of Medicine, The Journal of the American Medical Association, The Lancet, The Journal of the American College of Cardiology, Circulation, and European Heart Journal) from 1 January 1990 to 31 December 2018 and identified non-inferiority cardiovascular trials that used a surrogate marker as the primary endpoint. We assessed the non-inferiority margin reported in the manuscript and other publicly available platforms (e.g. protocol, clinicaltrials.gov). We also determined whether the included non-inferiority trials with surrogate markers as primary endpoints were followed by clinical outcome trials. Results We screened 15,553 publications and identified 247 cardiovascular trials that used a non-inferiority design. Of these, 37 had a surrogate marker as a primary endpoint (18 drug trials, 13 device trials, 6 others). All of these non-inferiority trials with surrogate outcomes were published after 2000, mostly in cardiology journals (13 in The Journal of the American College of Cardiology, 9 in European Heart Journal, 8 in Circulation, 6 in The Lancet, 1 in The New England Journal of Medicine), and their publication rate increased over time (p < 0.001 for linear trend). The median number of patients in the primary analysis was 300 (interquartile range: 202–465). The study protocol or a methods paper was publicly available for only 13 (35.1%) trials, of which the non-inferiority margin was not reported in 4 trials. In 16 studies (43.2%), the manuscript did not acknowledge the limitations of using a surrogate endpoint or the need for a definitive clinical outcome trial. Thirty-four trials (91.9%) concluded that the tested intervention met non-inferiority criteria. However, only five (13.5%) were followed by clinical outcomes trials the results of which did not always confirm non-inferiority. Conclusion Non-inferiority trials that use a surrogate marker as the primary endpoint are being increasingly performed. However, these trials pose particular challenges with design, reporting, and interpretation, which are not systematically and consistently addressed or reported.

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