In absence of vaccine and medications specifically designed to treat SARS-CoV-2 disease,identifying treatment options is critical at this time to control the disease outbreak.For this, we have designed a phase II trial of efficacy and safety with 3 branches ofdifferent combinations of treatment to identify which is the best early treatment optionfor patients with pneumonia due to SARS-CoV-2 (Covid-19) Identifying treatment options asearly as possible is critical to the SARS-CoV-2 outbreak response. Currently, there is noapproved vaccine for the disease and the treatments being used are not specificallydesigned for the SARS-CoV-2 virus, but are different groups of drugs used for otherpathologies with mechanisms of action that justify their use because they inhibit entryof the virus into virus cells or proteases.The study aims to compare Imatinib 400mg, Baricitinib 4mg or supportive treatment,administered for 7 days in the setting of SARS-CoV-2 pneumonia treatment.Patients who meet inclusion criteria and do not have any exclusion criteria will berandomized to receive open treatment 1:1:1
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. Latest evidence from the
UK RECOVERY and WHO SOLIDARITY trials suggest that antimalarials do not provide clinical
benefit in hospitalized patients with COVID-19.
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. The RECOVERY clinical
trial investigators have also reviewed the data concluding that LPV / r does not provide
clinical benefit in hospitalized patients with COVID-19.
Drug: Imatinib tablets
Imatinib 400 mg QD oral
Other Name: Arm A
Drug: Baricitinib Oral Tablet
Baricitinib 4 mg QD oral
Other Name: Arm B
Other: Supportive tratment
Any therapeutic intervention aimed at the control of clinical deterioration is
contemplated without initiating or having previously initiated any drug with potential
beneficial effect previously described in vitro or in pre-clinical / clinical models
against SARS-CoV-2 prior to patient recruitment.
Other Name: Best care
Inclusion Criteria:
- Signed informed consent form
- ≥18 years
- Confirmed diagnosis Pneumonia Covid19 + (Pneumonia confirmed radiologically and
positive test for detection of SARS-CoV-2 RNA in respiratory samples)
- ECOG functional state 0 or 1
- Less than 10 days from onset of symptoms saw.
- NO contraindication for medication
- ECG QT < < 440 ms males and < 460 ms females
- 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
Hospital Universitario de Fuenlabrada
Fuenlabrada, Madrid, Spain
David Bernal, Ph MD, Principal Investigator
Hospital Universitario de Fuenlabrada