COVID-19NCT04287686
Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19
A study testing Recombinant human angiotensin-converting enzyme 2 (rhACE2) in people with COVID-19, run by The First Affiliated Hospital of Guangzhou Medical University at 1 site in China.
Trial summary
This is an open label, randomized, controlled, pilot clinical study in patients with COVID-19, to obtain preliminary biologic, physiologic, and clinical data in patients with COVID-19 treated with rhACE2 or control patients, to help determine whether a subsequent Phase 2B trial is warranted. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Recombinant human angiotensin-converting enzyme 2 (rhACE2)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteChina
- Study dates
- Feb 2020to Apr 2020
- Phase
- Interventional
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Laboratory diagnosis:
- Respiratory specimen is positive for SARS-CoV-2 nucleic acid by RT-PCR; OR,
- The viral gene sequencing of the respiratory specimen is highly homologous to known novel coronavirus.
- Fever:
- Axillary temperature >37.3℃
- Respiratory variables (meets one of the following criteria):
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- Respiratory rate: RR ≥25 breaths/min
- Oxygen saturation ≤93% at rest on room air
- PaO2/FiO2 ≤300 mmHg（1 mmHg=0.133 KPa）
- Pulmonary imaging showed that the lesions progressed more than 50% within 24-48 hours, and the patients were managed as severe
- HBsAg negative, or HBV DNA ≤10^4 copy/ml if HBsAg positive; anti-HCV negative; HIV negative two weeks prior to signed Informed Consent Form (ICF)
- Appropriate ethics approval and
- ICF
Who cannot join
- Age <18 years; Age >80 years
- Pregnant or breast feeding woman or with positive pregnancy test result
- P/F <100 mmHg
- Moribund condition (death likely in days) or not expected to survive for >7 days
- Refusal by attending MD
- Not hemodynamically stable in the preceding 4 hours (MAP ≤65 mmHg, or SAP <90 mmHg, DAP <60 mmHg, vasoactive agents are required)
Show all 15Show fewer
- Patient on invasive mechanical ventilation or ECMO
- Patient in other therapeutic clinical trial within 30 days before ICF
- Receive any other ACE inhibitors (ACEI), angiotensin-receptor blockers (ARB) treatment within 7 days before ICF
- Chronic immunosuppression: current autoimmune diseases or patients who received immunotherapy within 30 days before ICF
- 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 liver failure, and ect)
- Known allergy to study drug or its ingredients related to renin-angiotensin system (RAS), or frequent and/or severe allergic reactions with multiple medications
- Other uncontrolled diseases, as judged by investigators
- Body weight ≥85 kg
Trial locations and contacts
1 site in 1 country.
China1 site
GCP Office of The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510120
About this study
Official title: A Randomized, Open Label, Controlled Clinical Study to Evaluate the Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) in Adult Patients With COVID-19
This is an open label, randomized, controlled, pilot clinical study in patients with COVID-19, to obtain preliminary biologic, physiologic, and clinical data in patients with COVID-19 treated with rhACE2 or control patients, to help determine whether a subsequent Phase 2B trial is warranted.
Read the detailed description
This is a small pilot study investigating whether there is any efficacy signal that warrants a larger Phase 2B trial, or any harm that suggests that such a trial should not be done. It is not expected to produce statistically significant results in the major endpoints. The investigators will examine all of the biologic, physiological, and clinical data to determine whether a Phase 2B trial is warranted.
Primary efficacy analysis will be carried only on patients receiving at least 4 doses of active drug. Safety analysis will be carried out on all patients receiving at least one dose of active drug.
It is planned to enroll more than or equal to 24 subjects with COVID-19. It is expected to have at least 12 evaluable patients in each group.
Experimental group: 0.4 mg/kg rhACE2 IV BID and standard of care Control group: standard of care
Intervention duration: up to 7 days of therapy
No planned interim analysis.
- Conditions
- COVID-19
- Being tested
- Recombinant human angiotensin-converting enzyme 2 (rhACE2)
- Keywords
- SARS-CoV-2, Renin-angiotensin-system (RAS)
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant human angiotensin-converting enzyme 2 (rhACE2)Drug
In this study, the experimental group will receive 0.4 mg/kg rhACE2 IV BID for 7 days.
| Study group | Role | What they receive |
|---|---|---|
| rhACE2 group | Experimental | 0.4 mg/kg IV BID for 7 days (unblinded) + standard of care Receives: Drug: Recombinant human angiotensin-converting enzyme 2 (rhACE2) |
| Control group | No intervention | Standard of care; no placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time course of body temperature (fever)
Compare the time course of body temperature (fever) between two groups over time.
Measured: 14 days
Viral load over time
Compare viral load between two groups over time.
Measured: 14 days
Secondary outcomes (25)
P/F ratio over time
PaO2/FiO2 ratio
Measured: 14 days
Sequential organ failure assessment score(SOFA score) over time
SOFA, including assessment of respiratory, blood, liver, circulatory, nerve, kidney, from 0 to 4 scores in each systems, the higher scores mean a worse outcome.
Measured: 14 days
Pulmonary Severity Index (PSI)
Measured: 14 days
Image examination of chest over time
Based on radiologist's assessment of inflammatory exudative disease, category as follows: significant improvement, partial improvement, no improvement, increase of partial exudation, significant increase in exudation, unable to judge.
Measured: 14 days
Proportion of subjects who progressed to critical illness or death
Measured: 14 days
Time from first dose to conversion to normal or mild pneumonia
Measured: 14 days
T-lymphocyte counts over time
Measured: 14 days
C-reactive protein levels over time
Measured: 14 days
Angiotensin II (Ang II) changes over time
Measured: 14 days
Angiotensin 1-7 (Ang 1-7) changes over time
Measured: 14 days
Angiotensin 1-5 (Ang 1-5) changes over time
Measured: 14 days
Renin changes over time
Measured: 14 days
Aldosterone changes over time
Measured: 14 days
Angiotensin-converting enzyme (ACE) changes over time
Measured: 14 days
Angiotensin-converting enzyme 2 (ACE2) changes over time
Measured: 14 days
Interleukin 6 (IL-6) changes over time
Measured: 14 days
Interleukin 8 (IL-8) changes over time
Measured: 14 days
Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time
Measured: 14 days
Plasminogen activator inhibitor type-1 (PAI-1) changes over time
Measured: 14 days
Von willebrand factor (vWF) changes over time
Measured: 14 days
Tumor necrosis factor-α (TNF-α) changes over time
Measured: 14 days
Soluble receptor for advanced glycation end products (sRAGE) changes over time
Measured: 14 days
Surfactant protein-D (SP-D) changes over time
Measured: 14 days
Angiopoietin-2 changes over time
Measured: 14 days
Frequency of adverse events and severe adverse events
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2020
- Study startFeb 2020 (estimated)
- Primary completionApr 2020 (estimated)
- Study completionApr 2020 (estimated)
Why it stopped: Without CDE Approval
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital of Guangzhou Medical UniversityThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2-arm pilot study
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yimin LI, The First Affiliated Hospital of Guangzhou Medical University
- Investigators
- Yimin Li, PhD, MD, Principal investigator, The First Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04287686
- Sponsor's protocol ID
- GIRH-APN01
- Status last verified
- Mar 2020
- First submitted
- 21 Feb 2020
- Last updated
- 17 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Zhang X, Li S, Niu S. ACE2 and COVID-19 and the resulting ARDS. Postgrad Med J. 2020 Jul;96(1137):403-407. doi: 10.1136/postgradmedj-2020-137935. Epub 2020 Jun 10.
PubMed 32522846
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open Label, Controlled Clinical Study to Evaluate the Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) in Adult Patients With COVID-19
- ClinicalTrials.gov ID
- NCT04287686
- Acronym / sponsor ID
- GIRH-APN01
- Conditions
- COVID-19
- Keywords
- SARS-CoV-2, Renin-angiotensin-system (RAS)
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Without CDE Approval
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The First Affiliated Hospital of Guangzhou Medical UniversityUniversity, hospital or other
- Study start
- Feb 2020 (estimated)
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Apr 2020 (estimated)
- First posted
- 27 Feb 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.
This is an open label, randomized, controlled, pilot clinical study in patients with COVID-19, to obtain preliminary biologic, physiologic, and clinical data in patients with COVID-19 treated with rhACE2 or control patients, to help determine whether a subsequent Phase 2B trial is warranted.
Detailed description
This is a small pilot study investigating whether there is any efficacy signal that warrants a larger Phase 2B trial, or any harm that suggests that such a trial should not be done. It is not expected to produce statistically significant results in the major endpoints. The investigators will examine all of the biologic, physiological, and clinical data to determine whether a Phase 2B trial is warranted.
Primary efficacy analysis will be carried only on patients receiving at least 4 doses of active drug. Safety analysis will be carried out on all patients receiving at least one dose of active drug.
It is planned to enroll more than or equal to 24 subjects with COVID-19. It is expected to have at least 12 evaluable patients in each group.
Experimental group: 0.4 mg/kg rhACE2 IV BID and standard of care Control group: standard of care
Intervention duration: up to 7 days of therapy
No planned interim analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 2-arm pilot study
| Arm | Type | Receives |
|---|---|---|
| rhACE2 group | Experimental | Drug: Recombinant human angiotensin-converting enzyme 2 (rhACE2)0.4 mg/kg IV BID for 7 days (unblinded) + standard of care |
| Control group | No intervention | –Standard of care; no placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Laboratory diagnosis:
- Fever:
- Axillary temperature >37.3℃
- Respiratory variables (meets one of the following criteria):
- HBsAg negative, or HBV DNA ≤10^4 copy/ml if HBsAg positive; anti-HCV negative; HIV negative two weeks prior to signed Informed Consent Form (ICF)
Key exclusion criteria (15 listed)
- Age <18 years; Age >80 years
- Pregnant or breast feeding woman or with positive pregnancy test result
- P/F <100 mmHg
- Moribund condition (death likely in days) or not expected to survive for >7 days
- Refusal by attending MD
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 |
|---|---|---|
| Recombinant human angiotensin-converting enzyme 2 (rhACE2)In this study, the experimental group will receive 0.4 mg/kg rhACE2 IV BID for 7 days. | Drug | rhACE2 group |
Primary outcome
Time course of body temperature (fever)
Time frame: 14 days
Compare the time course of body temperature (fever) between two groups over time.
Viral load over time
Time frame: 14 days
Compare viral load between two groups over time.
25 secondary outcomes
P/F ratio over time
Time frame: 14 days
Sequential organ failure assessment score(SOFA score) over time
Time frame: 14 days
Pulmonary Severity Index (PSI)
Time frame: 14 days
Image examination of chest over time
Time frame: 14 days
Proportion of subjects who progressed to critical illness or death
Time frame: 14 days
Time from first dose to conversion to normal or mild pneumonia
Time frame: 14 days
T-lymphocyte counts over time
Time frame: 14 days
C-reactive protein levels over time
Time frame: 14 days
Angiotensin II (Ang II) changes over time
Time frame: 14 days
Angiotensin 1-7 (Ang 1-7) changes over time
Time frame: 14 days
Angiotensin 1-5 (Ang 1-5) changes over time
Time frame: 14 days
Renin changes over time
Time frame: 14 days
Aldosterone changes over time
Time frame: 14 days
Angiotensin-converting enzyme (ACE) changes over time
Time frame: 14 days
Angiotensin-converting enzyme 2 (ACE2) changes over time
Time frame: 14 days
Interleukin 6 (IL-6) changes over time
Time frame: 14 days
Interleukin 8 (IL-8) changes over time
Time frame: 14 days
Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time
Time frame: 14 days
Plasminogen activator inhibitor type-1 (PAI-1) changes over time
Time frame: 14 days
Von willebrand factor (vWF) changes over time
Time frame: 14 days
Tumor necrosis factor-α (TNF-α) changes over time
Time frame: 14 days
Soluble receptor for advanced glycation end products (sRAGE) changes over time
Time frame: 14 days
Surfactant protein-D (SP-D) changes over time
Time frame: 14 days
Angiopoietin-2 changes over time
Time frame: 14 days
Frequency of adverse events and severe adverse events
Time frame: 14 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2020.
- Derived from this study: PubMed 32522846Zhang X, Li S, Niu S. ACE2 and COVID-19 and the resulting ARDS. Postgrad Med J. 2020 Jul;96(1137):403-407. doi: 10.1136/postgradmedj-2020-137935. Epub 2020 Jun 10.
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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.
Yimin Li, PhD, MD principal investigator
The First Affiliated Hospital of Guangzhou Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Recombinant human angiotensin-converting enzyme 2 (rhACE2) in people with COVID-19, run by The First Affiliated Hospital of Guangzhou Medical University at 1 site in China.
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 13 inclusion and 15 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: withdrawn, as of the sponsor's last update on 17 Mar 2020. 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 China. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time course of body temperature (fever) (time frame: 14 days). 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?
On the ClinicalTrials.gov record for NCT04287686, which also lists 1 linked publication.
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 17 Mar 2020.