Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies
Bikdeli B, Talasaz AH, Rashidi F, Sharif-Kashani B, Farrokhpour M, Bakhshandeh H, Sezavar H, Dabbagh A, Beigmohammadi MT, Payandemehr P, Yadollahzadeh M, Riahi T, Khalili H, Jamalkhani S, Rezaeifar P, Abedini A, Lookzadeh S, Shahmirzaei S, Tahamtan O, Matin S, Amin A, Parhizgar SE, Jimenez D, Gupta A, Madhavan MV, Parikh SA, Monreal M, Hadavand N, Hajighasemi A, Maleki M, Sadeghian S, Mohebbi B, Piazza G, Kirtane AJ, Lip GYH, Krumholz HM, Goldhaber SZ, Sadeghipour P. Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies. Thrombosis Research 2020, 196: 382-394. PMID: 32992075, PMCID: PMC7513771, DOI: 10.1016/j.thromres.2020.09.027.Peer-Reviewed Original ResearchConceptsStandard-dose prophylactic anticoagulationKey safety endpointIll patientsProphylactic anticoagulationVenous thromboembolismMajor bleedingSafety endpointCOVID-19Bleeding Academic Research Consortium definitionAcademic Research Consortium definitionsTimes upper normal limitAcute arterial thrombosisExuberant immune responseMacrovascular thrombotic eventsPrespecified secondary analysisCritically Ill PatientsKey secondary endpointVentilator-free daysExtracorporeal membrane oxygenationUpper normal limitNon-inferiority marginReverse transcription-polymerase chain reactionCoronavirus disease 2019Transcription-polymerase chain reactionAtorvastatin 20Non-inferiority trials using a surrogate marker as the primary endpoint: An increasing phenotype in cardiovascular trials
Bikdeli B, Caraballo C, Welsh J, Ross JS, Kaul S, Stone GW, Krumholz HM. Non-inferiority trials using a surrogate marker as the primary endpoint: An increasing phenotype in cardiovascular trials. Clinical Trials 2020, 17: 723-728. PMID: 32838556, PMCID: PMC8088773, DOI: 10.1177/1740774520949157.Peer-Reviewed Original ResearchConceptsNon-inferiority trialPrimary endpointClinical outcome trialsNon-inferiority marginSurrogate markerNon-inferiority designCardiovascular trialsOutcome trialsClinical outcomesDefinitive clinical outcome trialsNon-inferiority criteriaStudy protocolSurrogate outcomesBACKGROUND/Median numberSurrogate endpointsPrimary analysisCardiovascular interventionsCardiovascular medicineTrialsEndpointClinical interpretationOutcomesMarkersIntervention