Phase 2 ,double blind, randomized study of therapy with Angiotensin 1-7 in COVID-19patients. 120 confirmed SARS-CoV-2 infected patients who exhibit moderate- clinicalsymptoms including dyspnea, cough and fever, hospitalized in the KETER department inseveral hospitals in Israel, will be enrolled. 60 patients will receive Ang 1-7subcutaneously 500 mcg/kg /day. 60 patients will receive placebo : NaCl 0.9% 2 ml-control arm .Treatment duration: 14 days or until clinical improvement that enables discharge fromhospital.(the shortest time will be the limiting factor in treatment duration). Follow-up-30 days.14-30 days after discharge from hospital: we will contact the patient via phone to askquestions related to any possible adverse reaction to the drug and general health.
The working hypothesis behind this study is that the deleterious effects of SARS-CoV-2
are largely attributed to the deprivation of the affected target cells from their
advantageous ACE-2-Ang 1-7-MasR machinery on one hand, and to the use of ACE2 as a Trojan
horse to infect and destroy these cells on the other in a vicious feed-forward cycle.
120 confirmed SARS-CoV-2 infected patients who exhibit moderate- clinical symptoms
including dyspnea, cough and fever, hospitalized in the KETER department in several
hospitals in Israel, will be enrolled. 60 patients will receive Ang 1-7 subcutaneously
500 mcg/kg /day. 60 patients will receive placebo : NaCl 0.9% 2 ml -control arm .
Treatment duration: 14 days or until clinical improvement that enables discharge from
hospital.
All patients will be treated by Dexamethasone and Remdesivir, according to the published
guidelines. Moreover, if other promising medications will be approved for COVID-19, the
patients will also be treated by these medications. The current trial will not exclude
promising COVID-19 treatments.
Each patient will be closely followed up, where routine physical sings, respiratory and
hemodynamic parameters will be documented. In addition, the following complications will
be monitored: thromboembolic events, myocarditis, impaired liver function and acute
kidney injury. Allergic reactions will be treated by corticosteroids, antihistamines and
adrenalin if needed. Patients experiencing allergic reactions will be excluded from
continuing the trail.
In addition, biochemical (kidney function tests, electrolytes, liver enzymes, albumin,
protein, ferritin, troponin- 5 ml) and hematological (CBC-(3 ml), and coagulation
tests-(3 ml)) analysis will be performed on the day of enrollment and every 3 days .
Other blood tests for immunophenotyping, cytokines, COVID-19 PCR, Angiotensin II (Ang II)
levels, Angiotensin 1-7 (Ang 1-7) levels, ACE and ACE-2 will be collected at baseline and
at days 6,15,21 and 30 days after enrollment. and every week ( 2 chemistry (10 ml) and 2
CBC tubes (10 ml)).
In addition chest X-ray will be performed at enrollment and at days 6,15,21 and 30 days
after enrollment.
Drug: Angiotensin 1-7
Ang 1-7 subcutaneously 500 mcg/kg /day
Inclusion Criteria:
1. Respiratory specimen is positive for SARS-CoV-2 nucleic acid by RT-PCR
2. Fever: Temperature >37.8℃
3. Moderate lung disease, defined by the following respiratory variables (meets one of
the following criteria): lung infiltrates (evident by chest X-ray) not attributable
to other causes plus one of the following:
- Respiratory rate: RR ≥25 breaths/min
- Oxygen saturation ≤94 % at rest on room air
4. HBsAg negative, HCV negative; HIV negative
5. Informed consent
- Exclusion Criteria:
- Age <18 years
- Pregnant or breast-feeding woman or with positive pregnancy test result
- PaO2/FiO2 ≤100 mmHg / mechanical ventilation
- Severe organ failure - not expected to survive for >7 days
- Hemodynamically unstable in the preceding 10 hours (MAP ≤65 mmHg, or SAP <90
mmHg, DAP <60 mmHg, vasoactive agents are required)
- Patient on ECMO
- Patient in other therapeutic clinical trial within 30 days before enrolment
- Chronic immunosuppression: current autoimmune diseases or patients who received
immunotherapy within 30 days before enrolment
- Hematologic malignancy (lymphoma, leukemia, multiple myeloma)
- Other patient characteristics (not thought to be related to underlying
COVID-19) that portend a very poor prognosis (e.g, severe congestive heart
failure( NYHA class III or IV, EF less than 30%,) liver cirrhosis , chronic
kidney disease stave IV, V(e GFR<30 ml/min), chronic obstructive lung disease:
GOLD C,D : ≥2 exacerbations or ≥1 that required hospitalization, FEV1<50%, GOLD
3,4)
- Atopic patients suffering from allergies
Rambam Medical Center
Haifa, Israel
Investigator: Etty Kruzel-Davila, DR
Contact: +972-53-276-6052
e_kruzel@rambam.health.gov.il
Etty Kruzel-Davila, Dr.
+972-53-276-6052
e_kruzel@rambam.health.gov.il