SARS CoV 2 InfectionPhase 2/3ICASARSNCT05407597
Inhibition of Bradykinin in COVID-19 Infection With Icatibant
A Phase 2/3 study testing Icatibant and 0.9% Sodium Chloride Injection in people with SARS CoV 2 Infection, run by Belfast Health and Social Care Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SARS CoV 2 Infection
- What is being tested?
- Icatibant and 0.9% Sodium Chloride Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 16 May 2022to 7 Jul 2023
- Phase
- Phase 2/3
- 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
- Age >18 years.
- Documented evidence of COVID-19 and symptom onset of 7 days or less
- Acute hypoxia which will be defined as either low resting saturations <94% or supplementary oxygen to maintain oxygen saturations at >94%
Who cannot join
- Patients known to be pregnant or breastfeeding.
- Patients with unstable ischaemic heart disease or acute stroke
- Patients enrolled in other clinical trials of an investigational medicine within the previous 28 day period
- Patients who refuse to have blood samples taken.
- Known hypersensitivity to Icatibant
- 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).
- Patients with chronic heart or lung disease whose oxygen levels are reduced, but are unchanged from baseline
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Mater Infirmorum Hospital
Belfast, Antrim, BT14 6AB
About this study
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
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.
Read the 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
- Being tested
- Icatibant, 0.9% Sodium Chloride Injection
- Keywords
- Bradykinin, Alveolar-arterial gradient, Interleukin-6 (IL-6)
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IcatibantDrug
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.
0.9% Sodium Chloride InjectionDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Icatibant and Standard of care (SOC) | Active comparator | Icatibant will be given as a single, subcutaneous injection Receives: Drug: Icatibant |
| 0.9% Sodium Chloride and Standard of care (SOC) | Placebo comparator | Placebo will be given as a single, subcutaneous injection Receives: Drug: 0.9% Sodium Chloride Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Oxygenation
Alveolar-arterial gradient (Arterial blood gas sampling and FIO2 measurement)
Measured: Baseline and 3 hours after study drug administration
Secondary outcomes (3)
Change in Blood pressure
Systolic and diastolic blood pressure (mmHg)
Measured: Baseline and 3 hours after study drug administration
Change in mean arterial pressure (MAP)
Measurement of mean arterial pressure (mmHg)
Measured: Baseline and 3 hours after study drug administration
Change in heart rate
Measurement of pulse (beats/minute)
Measured: Baseline and 3 hours after study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2022
- Study start16 May 2022
- Primary completion9 Jun 2023
- Study completion7 Jul 2023
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 SARS CoV 2 InfectionStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomly allocated to receive either Icatibant (30mg) or 0.9% Sodium Chloride (3mls)
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Belfast Health and Social Care Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Queen's University, Belfast
- Responsible party
- Sponsor
- Investigators
- Joe Kidney, MD, Principal investigator, Belfast Health and Social Care Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05407597
- Sponsor's protocol ID
- 21036JK-AS
- Other IDs
- 2021-005851-35
- Acronym
- ICASARS
- Status last verified
- Sep 2023
- First submitted
- 11 May 2022
- Last updated
- 7 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38035747
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05407597
- Acronym / sponsor ID
- ICASARS / 21036JK-AS
- Conditions
- SARS CoV 2 Infection
- Keywords
- Bradykinin, Alveolar-arterial gradient, Interleukin-6 (IL-6)
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Belfast Health and Social Care TrustUniversity, hospital or other
- Collaborators
- Queen's University, Belfast
- Study start
- 16 May 2022 (actual)
- Primary completion
- 9 Jun 2023 (actual)
- Study completion
- 7 Jul 2023 (actual)
- First posted
- 7 Jun 2022 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Patients will be randomly allocated to receive either Icatibant (30mg) or 0.9% Sodium Chloride (3mls)
| Arm | Type | Receives |
|---|---|---|
| Icatibant and Standard of care (SOC) | Active comparator | Drug: IcatibantIcatibant will be given as a single, subcutaneous injection |
| 0.9% Sodium Chloride and Standard of care (SOC) | Placebo comparator | Drug: 0.9% Sodium Chloride InjectionPlacebo will be given as a single, subcutaneous injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age >18 years.
- Documented evidence of COVID-19 and symptom onset of 7 days or less
- Acute hypoxia which will be defined as either low resting saturations <94% or supplementary oxygen to maintain oxygen saturations at >94%
Key exclusion criteria (7 listed)
- Patients known to be pregnant or breastfeeding.
- Patients with unstable ischaemic heart disease or acute stroke
- Patients enrolled in other clinical trials of an investigational medicine within the previous 28 day period
- Patients who refuse to have blood samples taken.
- Known hypersensitivity to Icatibant
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 |
|---|---|---|
| IcatibantSolution 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 | Icatibant and Standard of care (SOC) |
| 0.9% Sodium Chloride InjectionSolution 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. | Drug | 0.9% Sodium Chloride and Standard of care (SOC) |
Primary outcome
Change in Oxygenation
Time frame: Baseline and 3 hours after study drug administration
Alveolar-arterial gradient (Arterial blood gas sampling and FIO2 measurement)
3 secondary outcomes
Change in Blood pressure
Time frame: Baseline and 3 hours after study drug administration
Change in mean arterial pressure (MAP)
Time frame: Baseline and 3 hours after study drug administration
Change in heart rate
Time frame: Baseline and 3 hours after study drug administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2023.
- Derived from this study: PubMed 38035747Bailey 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.
- 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.
Joe Kidney, MD principal investigator
Belfast Health and Social Care Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Icatibant and 0.9% Sodium Chloride Injection in people with SARS CoV 2 Infection, run by Belfast Health and Social Care Trust at 1 site in United Kingdom.
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 3 inclusion and 7 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: finished, as of the sponsor's last update on 7 Sep 2023. 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 United Kingdom. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Oxygenation (time frame: Baseline and 3 hours after study drug administration). 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 NCT05407597, 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 7 Sep 2023.