Treatment of Patients With Mild Coronavirus-19 (COVID-19) Disease With Methotrexate Associated to LDL Like Nanoparticles (Nano-COVID19)
NCT ID: NCT04610567
Last Updated: 2021-01-14
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
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UNKNOWN
PHASE1/PHASE2
100 participants
INTERVENTIONAL
2020-10-27
2021-07-15
Brief Summary
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A total of 100 patients will be randomized to receive MTX-LDE or placebo each 7 days, up to 3 times, during in hospital treatment.
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Detailed Description
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In phase 1, firstly 3 patients with moderate COVID-19 disease will receive MTX-LDE IV 15mg each 7 days, up to 3 times, during hospitalization. After that, 9 patients with moderate COVID-19 disease will receive MTX-LDE IV 30mg each 7 days, up to 3 times, during hospitalization. Follow-up assessments will occur daily following randomization during in hospital treatment and 2 weeks after discharge for evaluation of the occurrence of adverse events.The purpose of this phase will be evaluate safety and pharmacokinetics.
If no objection by data and safety monitoring board (DSMB), will be authorized to start the second phase.
In phase 2, 88 patients with moderate COVID-19 disease will be randomized to receive MTX-LDE IV 30mg or placebo-LDE IV each 7 days, up to 3 times, during hospitalization. Follow-up assessments will occur daily following randomization during in hospital treatment and 2 weeks after discharge for evaluation of the occurrence of any trial endpoints or other adverse events.The primary endpoint of this phase will be reduction in duration of hospitalization stay between groups.
Patients will undergo clinical and laboratory safety evaluations daily. An algorithm for drug suspension based on clinical and laboratory finding will be followed.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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MTX-LDE phase 1
Methotrexate carried by a lipid nanoparticle (MTX-LDE)
Methotrexate-LDE phase 1
3 patients will receive MTX-LDE at the dose of 15mg IV each 7 days during hospitalization, up to 3 times . After that, 9 patients will receive MTX-LDE at the dose of 30mg IV each 7 days during hospitalization, up to 3 times .
All patients will receive Leucovorin (calcium foliate) 25mg IV, 24hr after administration of MTX-LDE
MTX-LDE phase 2
Methotrexate carried by a lipid nanoparticle (MTX-LDE)
Methotrexate-LDE phase 2
44 patients will receive MTX-LDE at the dose of 30mg IV each 7 days during hospitalization, up to 3 times dose of 30mg IV each 7 days during hospitalization, up to 3 times . All patients will receive Leucovorin (calcium foliate) 25mg IV, 24hr after administration of MTX-LDE
Placebo-LDE phase 2
Lipid nanoparticle (LDE)
Placebo-LDE phase 2
44 patients will receive Placebo-LDE IV each 7 days during hospitalization, up to 3 times dose of 30mg IV each 7 days during hospitalization, up to 3 times . All patients will receive Leucovorin (calcium foliate) 25mg IV, 24hr after administration of Placebo-LDE
Interventions
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Methotrexate-LDE phase 1
3 patients will receive MTX-LDE at the dose of 15mg IV each 7 days during hospitalization, up to 3 times . After that, 9 patients will receive MTX-LDE at the dose of 30mg IV each 7 days during hospitalization, up to 3 times .
All patients will receive Leucovorin (calcium foliate) 25mg IV, 24hr after administration of MTX-LDE
Methotrexate-LDE phase 2
44 patients will receive MTX-LDE at the dose of 30mg IV each 7 days during hospitalization, up to 3 times dose of 30mg IV each 7 days during hospitalization, up to 3 times . All patients will receive Leucovorin (calcium foliate) 25mg IV, 24hr after administration of MTX-LDE
Placebo-LDE phase 2
44 patients will receive Placebo-LDE IV each 7 days during hospitalization, up to 3 times dose of 30mg IV each 7 days during hospitalization, up to 3 times . All patients will receive Leucovorin (calcium foliate) 25mg IV, 24hr after administration of Placebo-LDE
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Mild Coronavirus-19 disease (WHO Coronavirus-19 scale \< 5)
* Fewer than 14 days since symptom onset.
* Female patient is not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile.
* Female patient is of childbearing potential must has a negative pregnancy test.
* Signing the study informed consent.
Exclusion Criteria
* Need for oxygen supplementation via high-flow nasal cannula.
* Need for invasive mechanical ventilation.
* Extent of pulmonary involvement \> 50% by CT scan.
* Chronic renal failure (estimated glomerular filtration rate \<30 mL/min/1.73 m2)
* History of liver cirrhosis (Bilirubins levels \> 3mg/dl)
* History of heart failure ( Ejection fraction \<40%)
* History of Steven-Johnson disease
* History of stroke in the last 6 months
* History of sickle cell disease
* Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers.
* Prior history of chronic hepatitis B or C infection and known HIV positive.
* Patient undergoing chemotherapy for cancer
* Sepsis caused by fungal or multidrug resistant gram-negative bacteria
* Known allergy to methotrexate.
* Body mass index(BMI) \> 40 or \<18.5
* Pregnancy or breastfeeding.
* Patients enrolled in other clinical trials in the last 12 months
* Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
18 Years
85 Years
ALL
No
Sponsors
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Hospital Santa Marcelina
OTHER
University of Sao Paulo General Hospital
OTHER
Responsible Party
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Raul Cavalcante Maranhão
MD; PHD. Director Lipid Metabolism Laboratory, Heart Institute
Locations
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Heart Institute (InCor) - University of São Paulo Medical School, São Paulo, Brazil
São Paulo, São Paulo, Brazil
Hospital Santa Marcelina
São Paulo, São Paulo, Brazil
Institute Prevent Senior
São Paulo, São Paulo, Brazil
Countries
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Central Contacts
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Facility Contacts
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Jose Salvador Oliveira, MD;PhD
Role: primary
Rodrigo Esper, MD;PhD
Role: primary
References
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Liu PP, Blet A, Smyth D, Li H. The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulation. 2020 Jul 7;142(1):68-78. doi: 10.1161/CIRCULATIONAHA.120.047549. Epub 2020 Apr 15.
Solinas C, Perra L, Aiello M, Migliori E, Petrosillo N. A critical evaluation of glucocorticoids in the management of severe COVID-19. Cytokine Growth Factor Rev. 2020 Aug;54:8-23. doi: 10.1016/j.cytogfr.2020.06.012. Epub 2020 Jun 24.
Vinciguerra M, Romiti S, Fattouch K, De Bellis A, Greco E. Atherosclerosis as Pathogenetic Substrate for Sars-Cov2 Cytokine Storm. J Clin Med. 2020 Jul 3;9(7):2095. doi: 10.3390/jcm9072095.
Zhang S, Li L, Shen A, Chen Y, Qi Z. Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia. Clin Drug Investig. 2020 Jun;40(6):511-518. doi: 10.1007/s40261-020-00917-3.
Barbieri LR, Lourenco-Filho DD, Tavares ER, Carvalho PO, Gutierrez PS, Maranhao RC, Stolf NAG. Influence of Drugs Carried in Lipid Nanoparticles in Coronary Disease of Rabbit Transplanted Heart. Ann Thorac Surg. 2017 Aug;104(2):577-583. doi: 10.1016/j.athoracsur.2016.12.044. Epub 2017 Mar 24.
Bulgarelli A, Leite AC Jr, Dias AA, Maranhao RC. Anti-atherogenic effects of methotrexate carried by a lipid nanoemulsion that binds to LDL receptors in cholesterol-fed rabbits. Cardiovasc Drugs Ther. 2013 Dec;27(6):531-9. doi: 10.1007/s10557-013-6488-3.
Bulgarelli A, Martins Dias AA, Caramelli B, Maranhao RC. Treatment with methotrexate inhibits atherogenesis in cholesterol-fed rabbits. J Cardiovasc Pharmacol. 2012 Apr;59(4):308-14. doi: 10.1097/FJC.0b013e318241c385.
Maranhao RC, Tavares ER. Advances in non-invasive drug delivery for atherosclerotic heart disease. Expert Opin Drug Deliv. 2015 Jul;12(7):1135-47. doi: 10.1517/17425247.2015.999663. Epub 2015 Jan 14.
Maranhao RC, Guido MC, de Lima AD, Tavares ER, Marques AF, Tavares de Melo MD, Nicolau JC, Salemi VM, Kalil-Filho R. Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats. Int J Nanomedicine. 2017 May 17;12:3767-3784. doi: 10.2147/IJN.S129324. eCollection 2017.
Shah A, Kashyap R, Tosh P, Sampathkumar P, O'Horo JC. Guide to Understanding the 2019 Novel Coronavirus. Mayo Clin Proc. 2020 Apr;95(4):646-652. doi: 10.1016/j.mayocp.2020.02.003. Epub 2020 Feb 28. No abstract available.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.
Mitchell WB. Thromboinflammation in COVID-19 acute lung injury. Paediatr Respir Rev. 2020 Sep;35:20-24. doi: 10.1016/j.prrv.2020.06.004. Epub 2020 Jun 11.
Zhou Z, Guo D, Li C, Fang Z, Chen L, Yang R, Li X, Zeng W. Coronavirus disease 2019: initial chest CT findings. Eur Radiol. 2020 Aug;30(8):4398-4406. doi: 10.1007/s00330-020-06816-7. Epub 2020 Mar 24.
Cronstein BN. Molecular therapeutics. Methotrexate and its mechanism of action. Arthritis Rheum. 1996 Dec;39(12):1951-60. doi: 10.1002/art.1780391203. No abstract available.
Related Links
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WHO COVID-19 Therapeutic Trial Synopsis
Other Identifiers
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36746020.5.1001.0068
Identifier Type: -
Identifier Source: org_study_id
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