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.
Thromb Res
; 196: 382-394, 2020 12.
Artículo
en Inglés
| MEDLINE | ID: covidwho-791550
ABSTRACT
BACKGROUND:
Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown.METHODS:
The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19 An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count <20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes >3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts.CONCLUSIONS:
INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Trombosis
/
Enoxaparina
/
Inhibidores de Hidroximetilglutaril-CoA Reductasas
/
Tromboembolia Venosa
/
Atorvastatina
/
Tratamiento Farmacológico de COVID-19
/
Anticoagulantes
Tipo de estudio:
Estudio de cohorte
/
Estudios diagnósticos
/
Estudio experimental
/
Estudio observacional
/
Estudio pronóstico
/
Ensayo controlado aleatorizado
Tópicos:
Covid persistente
Límite:
Humanos
País/Región como asunto:
Asia
Idioma:
Inglés
Revista:
Thromb Res
Año:
2020
Tipo del documento:
Artículo
Similares
MEDLINE
...
LILACS
LIS