| Study characteristics |
| Methods |
Study design: single‐centre, open‐label, 2‐armed, parallel‐assignment RCT Type of publication: peer‐reviewed journal publication Setting and dates: hospital, April 2020‐July 2020 Country: Brazil Language: English Number of centres: 1 |
| Participants |
20 participants randomised (experimental (therapeutic anticoagulation) = 10; comparator (prophylactic anticoagulation) = 10), 20 participants analysed Mean age (years) ± SD: 55 ± 10 (experimental), 58 ± 16 (comparator) Gender (male/female): 9/11 (experimental), 7/13 (comparator) Severity of condition: all under mechanical ventilation Comorbidities (experimental/comparator): diabetes (4/3), hypertension (4/3), cardiovascular disease (1/1), immunocompromise (1/0) Confounding factors: prior anticoagulation (NR), surgery (NR), cancer (NR), antiplatelet use (NR), history of VTE (NR) BMI (kg/m²), mean ± SD: 33 ± 8 (experimental), 34 ± 8 (comparator) Anticoagulation before randomisation (experimental/comparator): prophylactic anticoagulation 4/7, therapeutic anticoagulation 0/0 Baseline medication (experimental/comparator): norepinephrine 6/6, neuromuscular blocking agent 10/10, corticosteroids 7/7, hydroxychloroquine 4/1, macrolide antibiotic 9/9, antiplatelet agents 0/0, remdesivir 0/0, interleukin‐6 inhibitors 0/0
Inclusion criteria
Age > 18 years‐old SARS‐CoV‐2 infection confirmed by RT‐PCR Presence of ARDS according to the Berlin definition Severe clinical presentation with respiratory failure requiring mechanical ventilation D‐dimer levels > 1000 μg/L Prothrombin time/INR < 1.5 aPTT ratio < 1.5 Platelet count > 100,000/mm³
Exclusion criteria
Age > 85 years‐old CrCl < 10 ml/min Severe circulatory shock with a dose of norepinephrine > 1.0 μg/kg/min Chronic renal failure in renal replacement therapy Child B and C chronic liver disease Advanced diseases, such as active cancer, heart failure with functional class III and IV (New York Heart Failure Association), COPD using home oxygen, advanced dementia, significant disability from stroke or severe head injury, cardiorespiratory arrest Pregnant women Recent major surgery or severe trauma in the last 3 weeks Recent stroke in the last 3 months Active bleeding Blood dyscrasia such as haemophilia, Von Willebrand factor deficiency Participation in another clinical investigation Indication for therapeutic anticoagulation due to PE, and ACS
|
| Interventions |
Experimental: therapeutic anticoagulation with heparin (subcutaneous enoxaparin with the dose according to age and adjusted daily by the CrCl estimated by the CKD Epidemiology Collaboration equation). The maximum dose of enoxaparin allowed was 140 mg twice daily. Comparator: subcutaneous UFH at a dose of 5000 IU three times/day (if weight < 120 kg) and 7500 IU three times/day (if weight > 120 kg) or enoxaparin at a dose of 40 mg once daily (if weight < 120 kg) and 40 mg twice daily (if weight > 120 kg) according to the doctor's judgment. Concomitant therapy: NR |
| Outcomes |
Primary (specified)
Primary (collected)
PaO2/FiO2 ratio Ventilator‐free days
Secondary (specified)
Plasma D‐dimer levels (D0, D4) Biomarkers of endothelial glycocalyx lesion levels (syndecan‐1; hyalurane; thrombomodulin; CD44s) between D0/D4 Endothelial glycocalyx thickness assessment assessed by sublingual microscopy using the Glycocheck equipment between D0/D4/D7/D14 Assessment of organ dysfunction assessed using the SOFA score between D0/D4 Overall 28‐day mortality
Secondary (collected)
Number of prone positioning sessions All‐cause 28‐day mortality In‐hospital mortality ICU‐free days Length of hospital stay Thrombotic events Adverse events Major bleeding Minor bleeding Bleeding requiring medical attention Drop in haemoglobin levels Drop in haemoglobin levels > 5.0 g/dL
Time points reported: at 0, 4, 7, 14 and 28 days after the start of the intervention |
| Notes |
Sponsor/funding: quote "This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors."; quote "Supporting source: Conselho Nacional de Pesquisa e Desenvolvimento tecnológico CNPq" (protocol) COIs: quote "all authors declare no conflicts of interest" Trial registration number: REBEC RBR‐949z6v |
| |
| Item |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Yes |
Quote "We used blocked randomisation, and the participants were randomised in a 1:1 ratio within two blocks of ten patients each." |
| Allocation concealment (selection bias) |
Yes |
Quote " The patients were assigned to each treatment by drawing the sequential numbering of opaque envelopes containing the treatment allocation." |
| Blinding of participants and personnel (performance bias) |
No |
Quote "In this randomised, controlled, open‐label..." |
| Blinding of outcome assessment (detection bias) |
No |
Quote "In this randomised, controlled, open‐label..." |
| Incomplete outcome data (attrition bias) |
No |
Quote "The third arm of this study with therapeutic intravenous unfractionated heparin (UFH) was abandoned due to difficulties in adjusting the activated partial thromboplastin time (aPTT) during the pandemic." |
| Selective reporting (reporting bias) |
Yes |
All prespecified outcomes were reported |
| Other bias |
Yes |
We do not suspect any other bias related to this study. |
