LitCovid-sentences  

PubMed:32586394 JSONTXT 13 Projects

Annnotations TAB TSV DIC JSON TextAE-old TextAE

Id Subject Object Predicate Lexical cue
T1 0-289 Sentence denotes Randomised controlled trial comparing efficacy and safety of high versus low Low-Molecular Weight Heparin dosages in hospitalized patients with severe COVID-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation (COVID-19 HD): a structured summary of a study protocol.
T2 290-301 Sentence denotes OBJECTIVES:
T3 302-721 Sentence denotes To assess whether high doses of Low Molecular Weight Heparin (LMWH) (i.e. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (i.e., Enoxaparin 4000 IU once day), in hospitalized patients with COVID19 not requiring Invasive Mechanical Ventilation [IMV], are: a)more effective in preventing clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first:
T4 722-1160 Sentence denotes 1.Death2.Acute Myocardial Infarction [AMI]3.Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were receiving standard oxygen therapy5.IMV in patients who at randomisation were receiving non-invasive mechanical ventilationb)Similar in terms of major bleeding risk TRIAL DESIGN:
T5 1161-1278 Sentence denotes Multicentre, randomised controlled, superiority, open label, parallel group, two arms (1:1 ratio), in-hospital study.
T6 1279-1292 Sentence denotes PARTICIPANTS:
T7 1293-1446 Sentence denotes Inpatients will be recruited from 7 Italian Academic and non-Academic Internal Medicine Units, 2 Infectious Disease Units and 1 Respiratory Disease Unit.
T8 1447-1481 Sentence denotes INCLUSION CRITERIA (ALL REQUIRED):
T9 1482-1484 Sentence denotes 1.
T10 1485-1511 Sentence denotes Age > 18 and < 80 years 2.
T11 1512-1591 Sentence denotes Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 3.
T12 1592-1790 Sentence denotes Severe pneumonia defined by the presence of at least one of the following criteria: a.Respiratory Rate ≥25 breaths /minb.Arterial oxygen saturation≤93% at rest on ambient airc.PaO2/FiO2 ≤300 mmHg 4.
T13 1791-1979 Sentence denotes Coagulopathy, defined by the presence of at least one of the following criteria: a.D-dimer >4 times the upper level of normal reference rangeb.Sepsis-Induced Coagulopathy (SIC) score >4 5.
T14 1980-2014 Sentence denotes No need of IMV EXCLUSION CRITERIA:
T15 2015-2017 Sentence denotes 1.
T16 2018-2042 Sentence denotes Age <18 and >80 years 2.
T17 2043-2049 Sentence denotes IMV 3.
T18 2050-2099 Sentence denotes Thrombocytopenia (platelet count < 80.000 mm3) 4.
T19 2100-2143 Sentence denotes Coagulopathy: INR >1.5, aPTT ratio > 1.4 5.
T20 2144-2231 Sentence denotes Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min) 6.
T21 2232-2271 Sentence denotes Known hypersensitivity to enoxaparin 7.
T22 2272-2318 Sentence denotes History of heparin induced thrombocytopenia 8.
T23 2319-2608 Sentence denotes Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations) 9.
T24 2609-2746 Sentence denotes Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves) 10.
T25 2747-2790 Sentence denotes Concomitant double antiplatelet therapy 11.
T26 2791-2961 Sentence denotes Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization; prophylactic doses are allowed 12.
T27 2962-3019 Sentence denotes Pregnancy or breastfeeding or positive pregnancy test 13.
T28 3020-3178 Sentence denotes Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) 14.
T29 3179-3246 Sentence denotes Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR:
T30 3247-3413 Sentence denotes Control Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at standard prophylactic dose (i.e., 4000 UI subcutaneously once day).
T31 3414-3587 Sentence denotes Intervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table.
T32 3588-3993 Sentence denotes This dose is commonly used in Italy when a bridging strategy is required for the management of surgery or invasive procedures in patients taking anti-vitamin K oral anticoagulants Body Weight (kg)Enoxaparin dose every 12 hours (IU)<50200050-69400070-89600090-1108000>11010000 The treatment with Enoxaparin will be initiated soon after randomization (maximum allowed starting time 12h after randomization).
T33 3994-4110 Sentence denotes The treatment will be administered every 12 hours in the intervention group and every 24 hours in the control group.
T34 4111-4229 Sentence denotes Treatments will be administered in the two arms until hospital discharge or the primary outcomes detailed below occur.
T35 4230-4244 Sentence denotes MAIN OUTCOMES:
T36 4245-4271 Sentence denotes Primary Efficacy Endpoint:
T37 4272-4381 Sentence denotes Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first:
T38 4382-4825 Sentence denotes 1.Death2.Acute Myocardial Infarction [AMI]3.Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were in standard oxygen therapy by delivery interfaces5.Need for IMV, in patients who at randomisation were in Cpap or NIV Time to the occurrence of each of these events will be recorded.
T39 4826-4913 Sentence denotes Clinical worsening will be analysed as a binary outcome as well as a time-to-event one.
T40 4914-4943 Sentence denotes Secondary Efficacy Endpoints:
T41 4944-5589 Sentence denotes Any of the following events occurring within the hospital stay 1.Death2.Acute Myocardial Infarction [AMI]3.Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were in standard oxygen therapy by delivery interfaces5.Need for IMV in patients who at randomisation were in Cpap or NIV6.Improvement of laboratory parameters of disease severity, including: o D-dimer levelo Plasma fibrinogen levelso Mean Platelet Volumeo Lymphocyte/Neutrophil ratioo IL-6 plasma levels MORTALITY AT 30 DAYS:
T42 5590-5712 Sentence denotes Information about patients' status will be sought in those who are discharged before 30 days on Day 30 from randomisation.
T43 5713-5777 Sentence denotes Time to the occurrence of each of these events will be recorded.
T44 5778-5863 Sentence denotes Each of these events will be analysed as a binary outcome and as a time-to-event one.
T45 5864-5888 Sentence denotes Primary safety endpoint:
T46 5889-5996 Sentence denotes Major bleeding, defined as an acute clinically overt bleeding associated with one or more of the following:
T47 5997-6619 Sentence denotes Decrease in haemoglobin of 2 g/dl or more;Transfusion of 2 or more units of packed red blood cells;Bleeding that occurs in at least one of the following critical sites [intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal];Bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death);Bleeding that necessitates surgical intervention Time to the occurrence of each of these events will be recorded.
T48 6620-6705 Sentence denotes Each of these events will be analysed as a binary outcome and as a time-to-event one.
T49 6706-6732 Sentence denotes Secondary safety endpoint:
T50 6733-6877 Sentence denotes Clinically Relevant non-major bleeding, defined as an acute clinically overt bleeding that does not meet the criteria for major and consists of:
T51 6878-7466 Sentence denotes 1.Any bleeding compromising hemodynamic2.Spontaneous hematoma larger than 25 cm2, or 100 cm2 if there was a traumatic cause3.Intramuscular hematoma documented by ultrasonography4.Epistaxis or gingival bleeding requiring tamponade or other medical intervention5.Bleeding from venipuncture for >5 minutes6.Haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures7.Haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention8.Any other bleeding requiring temporary cessation of a study drug.
T52 7467-7531 Sentence denotes Time to the occurrence of each of these events will be recorded.
T53 7532-7617 Sentence denotes Each of these events will be analysed as a binary outcome and as a time-to-event one.
T54 7618-7632 Sentence denotes RANDOMISATION:
T55 7633-7863 Sentence denotes Randomisation (with a 1:1 randomisation ratio) will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena.
T56 7864-7902 Sentence denotes Randomisation stratified by 4 factors:
T57 7903-8057 Sentence denotes 1) Gender (M/F); 2) Age (<75/≥75 years); 3) BMI (<30/≥30); 4) Comorbidities (0-1/>2) with random variable block sizes will be generated by STATA software.
T58 8058-8121 Sentence denotes The web-based system will guarantee the allocation concealment.
T59 8122-8276 Sentence denotes Blinding (masking) The study is conceived as open-label: patients and all health-care personnel involved in the study will be aware of the assigned group.
T60 8277-8316 Sentence denotes NUMBERS TO BE RANDOMISED (SAMPLE SIZE):
T61 8317-8478 Sentence denotes The target sample size is based on the hypothesis that LMWH administered at high doses versus low doses will significantly reduce the risk of clinical worsening.
T62 8479-8661 Sentence denotes The overall sample size in this study is expected to be 300 with 150 in the Low-Dose LMWH control group and 150 in the High-Dose LMWH intervention group, recruited over 10-11 months.
T63 8662-8941 Sentence denotes Assuming an alpha of 5% (two tailed) and a percentage of patients who experience clinical worsening in the control group being between 25% and 30%, the study will have 80% power to detect at least 50% relative reduction in the risk of death between low and high doses of heparin.
T64 8942-8955 Sentence denotes TRIAL STATUS:
T65 8956-8991 Sentence denotes Protocol version 1.2 of 11/05/2020.
T66 8992-9021 Sentence denotes Recruitment start (expected):
T67 9022-9063 Sentence denotes 08/06/2020 Recruitment finish (expected):
T68 9064-9271 Sentence denotes 30/04/2021 Trial registration EudraCT 2020-001972-13, registered on April 17th, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).
T69 9272-9452 Sentence denotes In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.