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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-005851-35 | EudraCT Number |
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| Name | Class |
|---|---|
| Queen's University, Belfast | OTHER |
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There is excess accumulation of bradykinin during symptomatic SARS CoV-2 lung infection. Bradykinin causes oedema in the lung, with reduced oxygen. It also causes vasodilation, hypotension and cytokine release.
In a normal reaction to a wound, such as after surgery, there is stimulation of pain nerves (called c-fibres), swelling and clotting. When people are hospitalized with COVID-19 they usually have a cough (lung c-fibre stimulation), swelling in the lung and clotting.
Bradykinin is a chemical that is released in response to inflammation. It causes C-fibre stimulation, dilation of vessels with oedema (swelling), lowered blood pressure and release of inflammatory cytokines. Normally the production of bradykinin is carefully balanced in the body. Some people have a tendency to release bradykinin. This results in spontaneous swelling - it is called hereditary episodic angioedema (HAE). There has been a treatment for HAE which has been in use since 2008. It is a medication called Icatibant. This blocks the effect of bradykinin at one of its receptors. It is given by injection under the skin. It has a short half life of approximately 1.5 hours.
The primary aim of the study is to see if treatment with Icatibant will improve blood oxygen levels. COVID-19 patients attending hospital with early symptom onset and low oxygen levels will screened for inclusion in the trial. Patients will be randomly allocated into one of two groups. One group will be given the study drug, Icatibant. The other group will be given a placebo injection containing saline water. Patients and research investigators will be blinded to treatment allocation.
Prior to receiving Icatibant/placebo, patients will have baseline measurements carried out. Blood pressure, Mean arterial pressure, heart rate, oxygen saturations and Fraction of inspired oxygen (FiO2) measurement will be carried out. Patients will undergo an arterial blood gas test. Part of the blood taken will be used for the measurement of interleukin-6 (IL-6) and part will be stored for future use. Patients will also have a retinal photograph of both eyes to assess the retinal vessel size. These measurements will be repeated 3 hours after receiving Icatibant/placebo.
A blood sample will also be taken from a group of control participants who do not have COVID-19 infection. The control blood samples will be analysed for IL-6 and part will also be stored for future use. The results will be compared to the baseline blood sample results taken from the COVID-19 positive trial patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Icatibant and Standard of care (SOC) | Active Comparator | Icatibant will be given as a single, subcutaneous injection |
|
| 0.9% Sodium Chloride and Standard of care (SOC) | Placebo Comparator | Placebo will be given as a single, subcutaneous injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Icatibant | Drug | Solution for injection, 30mg (3mls) administered as a single subcutaneous injection SARS CoV-2 patients will receive all supportive treatment and medications that are used as standard of care including but not limited to Dexamethasone, Remdesivir, Tocilizumab and antibiotics. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Oxygenation | Alveolar-arterial gradient (Arterial blood gas sampling and FIO2 measurement) | Baseline and 3 hours after study drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Blood pressure | Systolic and diastolic blood pressure (mmHg) | Baseline and 3 hours after study drug administration |
| Change in mean arterial pressure (MAP) | Measurement of mean arterial pressure (mmHg) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in interleukin-6 levels | Blood sample will be taken for measurement of serum IL-6 (pg/ml) | Baseline and 3 hours after study drug administration |
| Change in retinal vessel size (As measured by optical coherence tomography) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joe Kidney, MD | Belfast Health and Social Care Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mater Infirmorum Hospital | Belfast | Antrim | BT14 6AB | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38035747 | Derived | Bailey M, Linden D, Earley O, Guo Parke H, McAuley DF, Peto T, Taggart C, Kidney J. Inhibition of bradykinin in SARS-CoV-2 infection: a randomised, double-blind trial of icatibant compared with placebo (ICASARS). BMJ Open. 2023 Nov 30;13(11):e074726. doi: 10.1136/bmjopen-2023-074726. |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C065679 | icatibant |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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Patients will be randomly allocated to receive either Icatibant (30mg) or 0.9% Sodium Chloride (3mls)
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Patients and investigators will be blinded to treatment allocation. An unblinded research nurse will administer the study medication.
|
| 0.9% Sodium Chloride Injection | Drug | Solution for injection (3mls) administered as a single subcutaneous injection SARS CoV-2 patients will receive all supportive treatment and medications that are used as standard of care including but not limited to Dexamethasone, Remdesivir, Tocilizumab and antibiotics. |
|
| Baseline and 3 hours after study drug administration |
| Change in heart rate | Measurement of pulse (beats/minute) | Baseline and 3 hours after study drug administration |
OCT retinal imaging of both eyes. Retinal vasculature will be assessed.
| Baseline and 3 hours after study drug administration |
| Oxygen requirements and saturations 24 hours post study drug | Documentation of oxygen required and oxygen saturations | Approximately 24 hours after study drug administration |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D017670 |
| Sodium Compounds |