NCT05407597

Inhibition of Bradykinin in COVID-19 Infection With Icatibant

Prospective, Randomised, Double-blind Trial of Icatibant Compared to Placebo in Patients With Early Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) Infection

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Belfast Health and Social Care Trust · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• SARS CoV 2 Infection

Interventions

Type	Name	Description
DRUG	Icatibant	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.
DRUG	0.9% Sodium Chloride Injection	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.

Timeline

• Start date: 2022-05-16
• Primary completion: 2023-06-09
• Completion: 2023-07-07
• First posted: 2022-06-07
• Last updated: 2023-09-07

Locations

1 site across 1 country: United Kingdom