Clinical trial NCT05407597: Inhibition of Bradykinin in COVID-19 Infection With Icatibant
Official title: Prospective, Randomised, Double-blind Trial of Icatibant Compared to Placebo in Patients With Early Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SARS CoV 2 Infection
Keywords: Bradykinin
Alveolar-arterial gradient
Interleukin-6 (IL-6)
Lead sponsor: Belfast Health and Social Care Trust
Sponsor class: OTHER
Collaborators: name: Queen's University, Belfast
First posted: 2022-06-07
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomly allocated to receive either Icatibant (30mg) or 0.9% Sodium Chloride (3mls)
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. Age \>18 years.
2. Documented evidence of COVID-19 and symptom onset of 7 days or less
3. Acute hypoxia which will be defined as either low resting saturations \<94% or supplementary oxygen to maintain oxygen saturations at \>94%

Exclusion Criteria:

1. Patients known to be pregnant or breastfeeding.
2. Patients with unstable ischaemic heart disease or acute stroke
3. Patients enrolled in other clinical trials of an investigational medicine within the previous 28 day period
4. Patients who refuse to have blood samples taken.
5. Known hypersensitivity to Icatibant
6. Patients who at time of consent are likely to require imminent non-invasive/ invasive ventilatory support or patients already established on continuous positive airway pressure (CPAP).
7. Patients with chronic heart or lung disease whose oxygen levels are reduced, but are unchanged from baseline

Primary outcomes:
measure: Change in Oxygenation
timeFrame: Baseline and 3 hours after study drug administration
Secondary outcomes:
measure: Change in Blood pressure
timeFrame: Baseline and 3 hours after study drug administration
measure: Change in mean arterial pressure (MAP)
timeFrame: Baseline and 3 hours after study drug administration
measure: Change in heart rate
timeFrame: Baseline and 3 hours after study drug administration
Other outcomes:
measure: Change in interleukin-6 levels
timeFrame: Baseline and 3 hours after study drug administration
measure: Change in retinal vessel size (As measured by optical coherence tomography)
timeFrame: Baseline and 3 hours after study drug administration
measure: Oxygen requirements and saturations 24 hours post study drug
timeFrame: Approximately 24 hours after study drug administration
Locations:
city: Belfast
country: United Kingdom
facility: Mater Infirmorum Hospital
state: Antrim
Study officials:
affiliation: Belfast Health and Social Care Trust
name: Joe Kidney, MD
role: PRINCIPAL_INVESTIGATOR
References: