Ruxolitinib for Treatment of Covid-19 Induced Lung Injury ARDS
NCT ID: NCT04359290
Last Updated: 2021-08-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
15 participants
INTERVENTIONAL
2020-07-01
2021-07-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Ruxolitinib for the Treatment of Acute Respiratory Distress Syndrome in Patients With COVID-19 Infection
NCT04361903
Randomized, Controlled Study of IFX-1 in Patients With Severe COVID-19 Pneumonia
NCT04333420
Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With COVID-19 Lung Injury
NCT04341038
Efficacy and Safety of Tocilizumab in the Treatment of SARS-Cov-2 Related Pneumonia
NCT04332913
Proxalutamide Treatment for COVID-19 Patients in Intensive Care Unit
NCT04853927
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Ruxolitinib (INCB018424 phosphate, INC424, ruxolitinib phosphate) is a well established, potent and selective inhibitor of Janus kinase (JAK)1 and JAK2, with modest to marked selectivity against tyrosine kinase (TYK)2 and JAK3, respectively. Ruxolitinib interferes with the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function.
Ruxolitinib (JAKAVI®) is currently approved in the European Union (EU) for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (PMF) (also known as chronic idiopathic MF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF) and for the treatment of adult patients with PV who are resistant to or intolerant of hydroxyurea (HU). In the US, ruxolitinib has been approved in the treatment of steroid refractory graft versus host disease post allogeneic stem cell transplantation.
Because many patients with severe respiratory disease due to COVID-19 have features consistent with the cytokine release syndrome (CRS) and increased activation of the JAK/STAT pathway, it is postulated that ruxolitinib might have a useful role in treating these patients.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Ruxolitinib treatment
Ruxolitinib will be administered p.o. or by gavage feeding for max 28 days
Ruxolitinib administration
Ruxolitinib will be administered p.o. or by gavage feeding starting with 2 x 10mg or 2 x 15mg bid dose at day 1 according to the investigator's decision and can be increased up to 2 x 15mg bid from day 2 to day 28 (max) (depending on platelet counts and renal function). Ruxolitinib will be administered in the morning and evening. Dosing will be adjusted according to toxicity and kidney function.If the patient is discharged before day 28, the therapy will be discontinued for discharge.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Ruxolitinib administration
Ruxolitinib will be administered p.o. or by gavage feeding starting with 2 x 10mg or 2 x 15mg bid dose at day 1 according to the investigator's decision and can be increased up to 2 x 15mg bid from day 2 to day 28 (max) (depending on platelet counts and renal function). Ruxolitinib will be administered in the morning and evening. Dosing will be adjusted according to toxicity and kidney function.If the patient is discharged before day 28, the therapy will be discontinued for discharge.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay (result of the PCR is not necessary for inclusion, but has to approved latest within 48-72 hours after registration)
3. Willingness of men and women of childbearing potential to use highly effective contraceptive methods by abstinence or by using at least two contraceptive methods from the date of consent to the end of the study
4. severe lung disease as defined by following:
1. Recent intubation
2. Requirement of invasive ventilation moderate to severe pulmonary oxygen exchange disturbance as defined by (PaO2/FiO2) ≤ 200 mmHg at a PEEP ≥ 5mm H2O
3. Serum LDH \> 283 U/l
4. Ferritin above normal value
5. CT-scan: pulmonary infiltration compatible with Covid-19 disease
5. Patient or patient´s representative must provide written informed consent (and assent if applicable) before any study assessment is performed.
Exclusion Criteria
2. Active tuberculosis (result of positive tuberculosis infection is not necessary for exclusion, but has to approved later on during patient´s intervention)
3. Chronic kidney disease requiring dialysis
4. ALT/AST \> 5 times the upper limit of normal.
5. Pregnancy or breast feeding.
6. Allergy to study medication
7. Simultaneous participation in another clinical trial with an experimental treatment
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Philipps University Marburg
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Andreas Neubauer, Prof Dr.
Role: PRINCIPAL_INVESTIGATOR
Universitätsklinikum Giessen und Marburg (UKGM)
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Andreas Neubauer
Marburg, , Germany
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention. [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 10;41(2):145-151. doi: 10.3760/cma.j.issn.0254-6450.2020.02.003. Chinese.
Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.
Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults. Pediatr Pulmonol. 2020 May;55(5):1169-1174. doi: 10.1002/ppul.24718. Epub 2020 Mar 5.
Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang ZJ. Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China. JAMA. 2020 Apr 7;323(13):1313-1314. doi: 10.1001/jama.2020.2131.
[WHO] World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected [Resource on the internet]. 2020 [updated 13 March 2020; cited 24 March 2020]. Available from: https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected
An Insight of comparison between COVID-19 (2019-nCoV disease) and SARS in pathology and pathogenesis. Author: Xiaolong Cai; Internet posting, of 27-Feb-2020 retrieved 24-Mar-2020. Cite as DOI: 10.31219/osf.io/hw34x
Hermans MAW, Schrijver B, van Holten-Neelen CCPA, Gerth van Wijk R, van Hagen PM, van Daele PLA, Dik WA. The JAK1/JAK2- inhibitor ruxolitinib inhibits mast cell degranulation and cytokine release. Clin Exp Allergy. 2018 Nov;48(11):1412-1420. doi: 10.1111/cea.13217. Epub 2018 Aug 3.
Zhao J, Yu H, Liu Y, Gibson SA, Yan Z, Xu X, Gaggar A, Li PK, Li C, Wei S, Benveniste EN, Qin H. Protective effect of suppressing STAT3 activity in LPS-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2016 Nov 1;311(5):L868-L880. doi: 10.1152/ajplung.00281.2016. Epub 2016 Sep 16.
Coon TA, McKelvey AC, Lear T, Rajbhandari S, Dunn SR, Connelly W, Zhao JY, Han S, Liu Y, Weathington NM, McVerry BJ, Zhang Y, Chen BB. The proinflammatory role of HECTD2 in innate immunity and experimental lung injury. Sci Transl Med. 2015 Jul 8;7(295):295ra109. doi: 10.1126/scitranslmed.aab3881.
Ruxolitinib Prevents Cytokine Release Syndrome after CART Cell Therapy without Impairing the Anti-Tumor Effect in a Xenograft Model Saad S Kenderian, MD , Blood (2016) 128 (22): 652
Calbet M, Ramis I, Calama E, Carreno C, Paris S, Maldonado M, Orellana A, Calaf E, Pauta M, De Alba J, Bach J, Miralpeix M. Novel Inhaled Pan-JAK Inhibitor, LAS194046, Reduces Allergen-Induced Airway Inflammation, Late Asthmatic Response, and pSTAT Activation in Brown Norway Rats. J Pharmacol Exp Ther. 2019 Aug;370(2):137-147. doi: 10.1124/jpet.119.256263. Epub 2019 May 13.
The definition and risks of Cytokine Release Syndrome-Like in 11 COVID-19-Infected Pneumonia critically ill patients: Disease Characteristics and Retrospective Analysis Wenjun Wang Jr. et al Internet posting of 27-Feb-2020 retrieved 24-Mar-2020 Cite as: https://doi.org/10.1101/2020.02.26.20026989
Hoffmann J, Machado D, Terrier O, Pouzol S, Messaoudi M, Basualdo W, Espinola EE, Guillen RM, Rosa-Calatrava M, Picot V, Benet T, Endtz H, Russomando G, Paranhos-Baccala G. Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study. Sci Rep. 2016 Dec 6;6:38532. doi: 10.1038/srep38532.
Neubauer A, Johow J, Mack E, Burchert A, Meyn D, Kadlubiec A, Torje I, Wulf H, Vogelmeier CF, Hoyer J, Skevaki C, Muellenbach RM, Keller C, Schade-Brittinger C, Rolfes C, Wiesmann T. The janus-kinase inhibitor ruxolitinib in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS). Leukemia. 2021 Oct;35(10):2917-2923. doi: 10.1038/s41375-021-01374-3. Epub 2021 Aug 12.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
KKS-278
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.