Enoxaparin Thromboprophylaxis in Children Hospitalized for COVID-19: A Phase 2 Trial.


Journal

Pediatrics
ISSN: 1098-4275
Titre abrégé: Pediatrics
Pays: United States
ID NLM: 0376422

Informations de publication

Date de publication:
01 07 2022
Historique:
accepted: 22 04 2022
pubmed: 30 4 2022
medline: 6 7 2022
entrez: 29 4 2022
Statut: ppublish

Résumé

Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19, including primary respiratory infection and multisystem inflammatory syndrome in children (MISC). We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg per dose; max: 60mg; target anti-Xa activity: 0.20-0.49IU/mL) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; enoxaparin dose-requirements; and cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by participant age (±12 years) and clinical presentation. Forty children were enrolled and 38 met analyses criteria. None experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P = .51) but was greater for participants with MISC (0.52 [0.5-0.61] mg/kg) as compared with primary COVID-19 (0.48 [0.39-0.51] mg/kg, P = .010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention. Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.

Sections du résumé

BACKGROUND
Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19, including primary respiratory infection and multisystem inflammatory syndrome in children (MISC).
METHODS
We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg per dose; max: 60mg; target anti-Xa activity: 0.20-0.49IU/mL) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; enoxaparin dose-requirements; and cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by participant age (±12 years) and clinical presentation.
RESULTS
Forty children were enrolled and 38 met analyses criteria. None experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P = .51) but was greater for participants with MISC (0.52 [0.5-0.61] mg/kg) as compared with primary COVID-19 (0.48 [0.39-0.51] mg/kg, P = .010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention.
CONCLUSIONS
Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.

Identifiants

pubmed: 35484817
pii: 186936
doi: 10.1542/peds.2022-056726
pii:
doi:

Substances chimiques

Anticoagulants 0
Enoxaparin 0

Banques de données

ClinicalTrials.gov
['NCT04354155']

Types de publication

Clinical Trial, Phase II Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2022 by the American Academy of Pediatrics.

Auteurs

Anthony A Sochet (AA)

Departments of Anesthesia.
Critical Care Medicine.

John M Morrison (JM)

Departments of Anesthesia.
Pediatrics.

Julie Jaffray (J)

Department of Pediatrics, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California.

Nihal Godiwala (N)

Department of Pediatrics, Louisiana State University School of Medicine, New Orleans, Louisiana.

Hope P Wilson (HP)

Department of Pediatrics, University of Alabama School of Medicine, Birmingham, Alabama.

Courtney D Thornburg (CD)

Department of Pediatrics, University of California San Diego, La Jolla, California Division of Hematology and Oncology, Rady Children's Hospital San Diego, San Diego, California.

Rukhmi V Bhat (RV)

Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Ayesha Zia (A)

Department of Pediatrics, The University of Texas Southwestern, Dallas, Texas.

Courtney Lawrence (C)

Pediatrics.
Pathology.

Sapna R Kudchadkar (SR)

Critical Care Medicine.
Pediatrics.
Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Frances Hamblin (F)

Departments of Anesthesia.

Christopher J Russell (CJ)

Department of Pediatrics, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California.

Alex C Spyropoulos (AC)

Department of Medicine, Zucker School of Medicine at Hofstra and Northwell and Feinstein Institutes for Medical Research, Manhasset, New York.
Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.

Ernest K Amankwah (EK)

Departments of Anesthesia.
Pediatrics.
Oncology, Johns Hopkins All Children's Institute for Clinical and Translational Research.

Neil A Goldenberg (NA)

Departments of Anesthesia.
Pediatrics.
Medicine.

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Classifications MeSH