Clinical Trial to Evaluate Efficacy of 3 Types of Treatment in Patients With Pneumonia by COVID-19
Kľúčové slová
Abstrakt
Popis
Identifying treatment options is critical to the SARS-CoV-2 outbreak response. Currently there is no vaccine and treatments used are not specifically designed for this virus; They are drugs used for other pathologies. We have identified possible drugs with a known safety profile, selected the most promising ones and designed 3 combinations to select the one with the best results in clinical improvement of pneumonia due to Covid-19.
-Virus entry inhibitors: broad spectrum antivirals (antimalarials). They block viral infection by increasing endosomal pH necessary for virus / cell fusion, as well as interfering with glycosylation of cellular SARS-CoV receptors. It also has immunomodulatory activity, which can enhance antiviral effect. Hydroxychloroquine more powerful than chloroquine.
Baricitinib, Janus kinase inhibitor, showing high affinity for AAK1. Disruption of AAK1 (one of the known regulators of viral endocytosis) could block passage of SARS-CoV-2 to cells and also the intracellular assembly of virus particles. Furthermore, it has the capacity to bind cyclin G-associated kinase, another regulator of endocytosis. You can limit systemic inflammatory response and cytokine production by inhibiting the JAK-STAT32 pathway.
Imatinib; Antitumor agent inhibitory activity of some tirsin kinases (TK), especially fusion oncoprotein BCR-ABL1, c-kit and native kinase ABL1. It has shown antiviral properties in early stages of infection against SARS-CoV and MERS-CoV, phylogenetically related to SARS-CoV2. In addition, it has been linked to reduced inflammation and improved endothelial barrier and pulmonary edema.
-Protease inhibitors: lopinavir / ritonavir (HIV treatment); expected interactions with SARS-CoV-2 proteases; The therapeutic effect of ritonavir and lopinavir could be mainly due to its inhibitory effect on coronavirus endopeptidase C30.
Termíny
| Naposledy overené: | 03/31/2020 |
| Prvý príspevok: | 04/06/2020 |
| Odhadovaná registrácia bola odoslaná: | 04/10/2020 |
| Prvý príspevok: | 04/14/2020 |
| Posledná aktualizácia bola odoslaná: | 05/06/2020 |
| Posledná aktualizácia bola zverejnená: | 05/07/2020 |
| Aktuálny dátum začatia štúdie: | 04/12/2020 |
| Odhadovaný dátum dokončenia primárneho okruhu: | 07/31/2020 |
| Odhadovaný dátum dokončenia štúdie: | 08/31/2020 |
Stav alebo choroba
Intervencia / liečba
Drug: Hidroxicloroquine
Drug: Lopinavir/ Ritonavir 400 mg
Drug: Imatinib 400 mg
Drug: Baricitinib 4 mg
Fáza
Skupiny zbraní
| Arm | Intervencia / liečba |
|---|---|
| Experimental: Lopinavir/ Ritonavir 400 mg Hidroxicloroquina 200mg 1 tablet every 12 hours Lopinavir/ Ritonavir 200/50 mg 1 tablet 12 hours | Drug: Lopinavir/ Ritonavir 400 mg Lopinavir/ritonavir 200/50 mg BID oral |
| Experimental: Imatinib 400 mg Hidroxicloroquina 200mg 1 tablet every 12 hours Imatinib 400 mg 1 tablet 24 hours | Drug: Imatinib 400 mg Imatinib 400 mg QD oral |
| Experimental: Baricitinib 4 mg Hidroxicloroquina 200mg 1 tablet every 12 hours Baricitinib 4 mg 1 tablet 24 hours | Drug: Baricitinib 4 mg Baricitinib 4 mg QD oral |
Kritériá oprávnenosti
| Vek vhodný na štúdium | 18 Years To 18 Years |
| Pohlavia vhodné na štúdium | All |
| Prijíma zdravých dobrovoľníkov | Áno |
| Kritériá | Inclusion Criteria: - Signed informed consent form - ≥18 years - Confirmed diagnosis Pneumonia Covid19 positive - ECOG functional state 0 or 1 - Less than 7 days from onset of symptoms saw. - NO contraindication for medication - ECG QT <0.4 - Adequate liver, kidney and hematological function (or within the safety range to use these drugs): 1. Absolute granulocyte count> 1.5 x 109 / L 2. Absolute platelet count> 100 x 109 / L 3. Hb> 10 g / dL 4. Cr <1.5 mg / dL or Clearance> 50mL / min 5. Bilirubin <3 ULN 6. AST / ALT ≤ 2.5 times ULN Exclusion Criteria: - No Covid confirmation - No pneumonia - Previous treatment with any of the study drugs - Concomitant serious medical condition: 1. Congestive Heart failure 2. Acute myocardial infarction 6 months prior 3. Unstable Angina 4. Cardiomyopathy 5. Unstable Ventricular Arrhythmia 6. Uncontrolled Hypertension 7. Uncontrolled psychotic disorders 8. Serious active infections 9. HIV infections 10. Active hepatitis 11. Neoplasia in active cancer treatment - Inability to take oral medication or malabsorption syndrome saw. - Inability to comply with study and follow-up procedures - History of only relevant thromboembolic or hemorrhagic episodes in the last 6 months - Contraindication to any study medication - Pregnant women |
Výsledok
Primárne výstupné opatrenia
1. time to clinical improvement [baseline to day 14]
Opatrenia sekundárnych výsledkov
1. Safety of treatments [through study completion, an average of 1 month]
2. Tolerability of treatments [during treatment and up to 30 days after the last treatment dose]
Ostatné výstupné opatrenia
1. Biomarkers and genetic markers of susceptibility to SARS-CoV-2 [baseline]
