COVID-19Phase 2NCT04605887
Angiotensin 1-7 as a Therapy in the Treatment of COVID-19
A Phase 2 study testing Angiotensin 1-7 in people with COVID-19, run by Rambam Health Care Campus at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Angiotensin 1-7
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteIsrael
- Study dates
- 18 Jan 2021to Apr 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Respiratory specimen is positive for SARS-CoV-2 nucleic acid by RT-PCR
- Fever: Temperature >37.8℃
- 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
- HBsAg negative, HCV negative; HIV negative
- Informed consent
- -
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Rambam Medical Center
Haifa, 3525408
Etty Kruzel-Davila, DR, +972-53-276-6052, e_kruzel@rambam.health.gov.il
About this study
Official title: Angiotensin 1-7 as a Therapy for Pneumonia Caused by Coronavirus 2(SARS-CoV-2)
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.
Read the 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.
- Conditions
- COVID-19
- Being tested
- Angiotensin 1-7
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin 1-7Drug
Ang 1-7 subcutaneously 500 mcg/kg /day
| Study group | Role | What they receive |
|---|---|---|
| treatment group | Active comparator | Ang 1-7 subcutaneously 500 mcg/kg /day Receives: Drug: Angiotensin 1-7 |
| control group | Placebo comparator | NaCl 0.9% subcutaneously 2.0 cc once a day Receives: Drug: Angiotensin 1-7 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Need for mechanical ventilation
Patient is intubated
Measured: Any time from randomization up to 30 days of last study treatment dose
Death
death certificate
Measured: Any time from randomization up to 30 days of last study treatment dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2020
- Study start18 Jan 2021
- Primary completionNov 2023 (estimated)
- Study completionApr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Collaborators
- Constant Therapeutics LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04605887
- Sponsor's protocol ID
- 0328-20-RMB
- Other IDs
- MOH_2020-11-02_009463
- Status last verified
- Jan 2021
- First submitted
- 27 Oct 2020
- Last updated
- 22 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Angiotensin 1-7 as a Therapy for Pneumonia Caused by Coronavirus 2(SARS-CoV-2)
- ClinicalTrials.gov ID
- NCT04605887
- Acronym / sponsor ID
- 0328-20-RMB
- Conditions
- COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Rambam Health Care CampusUniversity, hospital or other
- Collaborators
- Constant Therapeutics LLC
- Study start
- 18 Jan 2021 (actual)
- Primary completion
- Nov 2023 (estimated)
- Study completion
- Apr 2024 (estimated)
- First posted
- 28 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| treatment group | Active comparator | Drug: Angiotensin 1-7Ang 1-7 subcutaneously 500 mcg/kg /day |
| control group | Placebo comparator | Drug: Angiotensin 1-7NaCl 0.9% subcutaneously 2.0 cc once a day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Respiratory specimen is positive for SARS-CoV-2 nucleic acid by RT-PCR
- Fever: Temperature >37.8℃
- 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:
- HBsAg negative, HCV negative; HIV negative
- Informed consent
Key exclusion criteria (11 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angiotensin 1-7Ang 1-7 subcutaneously 500 mcg/kg /day | Drug | control group, treatment group |
Primary outcome
Need for mechanical ventilation
Time frame: Any time from randomization up to 30 days of last study treatment dose
Patient is intubated
Death
Time frame: Any time from randomization up to 30 days of last study treatment dose
death certificate
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Angiotensin 1-7 in people with COVID-19, run by Rambam Health Care Campus at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Etty Kruzel-Davila, Dr. (+972-53-276-6052, e_kruzel@rambam.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Need for mechanical ventilation (time frame: Any time from randomization up to 30 days of last study treatment dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2021.