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Angiotensin 1-7 as a Therapy in the Treatment of COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04605887
Recruitment Status : Recruiting
First Posted : October 28, 2020
Last Update Posted : January 22, 2021
Sponsor:
Collaborator:
Constant Therapeutics LLC
Information provided by (Responsible Party):
Rambam Health Care Campus

Study Description
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Brief Summary:

Phase 2 ,double blind, randomized study of therapy with Angiotensin 1-7 in COVID-19 patients. 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.

(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 ask questions related to any possible adverse reaction to the drug and general health.


Condition or disease Intervention/treatment Phase
COVID-19 Drug: Angiotensin 1-7 Phase 2

Detailed Description:

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Angiotensin 1-7 as a Therapy for Pneumonia Caused by Coronavirus 2(SARS-CoV-2)
Actual Study Start Date : January 18, 2021
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: treatment group
Ang 1-7 subcutaneously 500 mcg/kg /day
 Drug: Angiotensin 1-7
Ang 1-7 subcutaneously 500 mcg/kg /day
Placebo Comparator: control group
NaCl 0.9% subcutaneously 2.0 cc once a day
 Drug: Angiotensin 1-7
Ang 1-7 subcutaneously 500 mcg/kg /day


Outcome Measures
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Primary Outcome Measures :
  1. Need for mechanical ventilation [ Time Frame: Any time from randomization up to 30 days of last study treatment dose ]
    Patient is intubated

  2. Death [ Time Frame: Any time from randomization up to 30 days of last study treatment dose ]
    death certificate


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04605887


Contacts
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Contact: Etty Kruzel-Davila, Dr. +972-53-276-6052 e_kruzel@rambam.health.gov.il

Locations
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Israel
Rambam Medical Center Recruiting
Haifa, Israel, 3525408
Contact: Etty Kruzel-Davila, DR    +972-53-276-6052    e_kruzel@rambam.health.gov.il   
Sponsors and Collaborators
Rambam Health Care Campus
Constant Therapeutics LLC
More Information
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Responsible Party: Rambam Health Care Campus
ClinicalTrials.gov Identifier: NCT04605887    
Other Study ID Numbers: 0328-20-RMB
MOH_2020-11-02_009463 ( Other Identifier: Ministry Of Health Israel )
First Posted: October 28, 2020    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
 Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Angiotensin I (1-7)
Antihypertensive Agents
Vasodilator Agents