AngioedemaPhase 2NCT01154361
AMelioration of Angiotensin Converting Enzyme Inhibitor Induced Angioedema Study
A Phase 2 study testing Icatibant (subcutaneous) and plazebo (intravenous) and Cortisone + Clemastin (intravenous) and plazebo (subcutaneous) in people with Angioedema, run by Technical University of Munich at 1 site in Germany.
Trial summary
This is a multicenter study recruiting patients with angioedema induced by ACEI. Open-label treatment with subcutaneous Icatibant compared to a historic group of 47 patients with ACE inhibitor induced angioedema which the investigators have been previously treated in the investigators centers with current "standard"… Read more about this study
- Who is it for?
- Ages 18 to 84 years
- Conditions the study is for
- Angioedema
- What is being tested?
- Icatibant (subcutaneous) and plazebo (intravenous) and Cortisone + Clemastin (intravenous) and plazebo (subcutaneous)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- Not given
- Where
- 1 siteGermany
- Study dates
- Start not givento not given
- Phase
- Phase 2
- 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 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 <85 years
- Patient is currently treated with an ACEI
- Patient must have acute angioedema attack caused by an ACEI
- Treatment should be administrated within 10 hrs after onset by an ACEI
- Patient with angioedema of head and /or neck (face, lips, cheeks, tongue, soft palate/uvula, pharynx and larynx)
- At least one moderate to severe severe angioedema symptom as assessed by the investigator, requiring a medical intervention
- Signed written Informed Consent Form
Who cannot join
- Diagnosis of angioedema that was not caused by ACEI: e.g. hereditary angioedema (C1-INH deficiency), allergy, anaphylaxis, insect bite, trauma, infection, abscess, tumor, post-radiation or post-operative or processes related to salivary glands and others where it is unlikely that the ACEI is causing the angioedema
- Participation in a clinical trial of another investigational medicinal product (IMP) within 30 days
- Patients with acute urticaria
- Patients with a medical history of any angioedema before taking an ACEI
- Patients with an acute rash or hives in the face or somewhere else
- Unstable angina or acute myocardial infarction
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- Acute heart failure
- Serious concomitant illnesses that the physician considers to be a contraindication for participation in the trial
- Pregnancy and/or breast-feeding
- Mental condition rendering the patients, in the opinion of the investigator, unable to understand the nature, scope and possible consequences of the study;
- Unlikely to comply with the protocol, e.g., uncooperative attitude, inability to return for the follow-up visit, or unlikely to complete the study for any reason.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Klinikum rechts der Isar Hals-Nasen-Ohrenklinik der TUM
Munich, Bavaria, 81675
About this study
Official title: A Multicenter Study, Randomized, Double-blind With 2 Groups as Prove of Concept for the Treatment of ACEI Induced Angioedema With Subcutaneous Icatibant
This is a multicenter study recruiting patients with angioedema induced by ACEI.
Open-label treatment with subcutaneous Icatibant compared to a historic group of 47 patients with ACE inhibitor induced angioedema which the investigators have been previously treated in the investigators centers with current "standard" therapy (250 mg methylprednisolon and 2 mg clemastine).
In cases with fast progression of edema after application the study-drug, a second application with icatibant could be necessary. Rescue medication and intervention.
Read the detailed description
Sudden occurrence of subcutaneous or submucosal non-itchy swelling, so-called angioedema, is a well known side effect of angiotensin-converting enzyme inhibitors (ACEi), which may become life-threatening if the upper airway is involved. To be note, ACEi induced angioedema were always located in the head and neck region.
The pathophysiology of ACE inhibitor (ACEi) induced angioedema most likely resembles that of hereditary angioedema (HAE), i.e. it is mainly mediated by bradykinin induced activation of vascular bradykinin B2 receptors (BKR-2). In contrast to an increased bradykinin generation in HAE, treatment with ACEi decreases the bradykinin degradation in plasma and increases the biological activity of bradykinin.
The current pharmacotherapy of ACEi induced angioedema is not satisfactory. Antihistamines and corticosteroids may be effective in the treatment of urticaria with cutaneous edema and itchy, but are theoretically ineffective and hence superfluous in bradykinin induced angioedema. However, glucocorticoids still belong to the standard treatment of angioedema.
We hypothesized that the BKR-2 antagonist icatibant might be an effective therapy for ACEi-induced angioedema.
Patients with ACEi induced angioedema, located in the upper aero-digestive tract will be randomized and treated either with icatibant and plazebo or cortisone with clemastin and plazebo.
- Conditions
- Angioedema
- Being tested
- Icatibant (subcutaneous) and plazebo (intravenous), Cortisone + Clemastin (intravenous) and plazebo (subcutaneous)
- Keywords
- ACE inhibitor induced angioedema, Bradykinin, Non-itching edema, Non-allergic angioedema, Quincke edema, Drug induced angioedema, Bradykinin B2 receptor antagonist, Icatibant, HOE 140
- Medical subject headings
- Angioedema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Icatibant (subcutaneous) and plazebo (intravenous)Drug
Cortisone + Clemastin (intravenous) and plazebo (subcutaneous)Drug
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Not described Receives: Drug: Icatibant (subcutaneous) and plazebo (intravenous) |
| Arm B | Active comparator | Not described Receives: Drug: Cortisone + Clemastin (intravenous) and plazebo (subcutaneous) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to complete resolution of angioedema
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2010 (estimated)
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 AngioedemaStudies of the same condition, open and under way.
- More trials run by Technical University of MunichThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
Sponsor and investigators
- Lead sponsor
- Technical University of Munich
- Sponsor type
- University, hospital or other
- Investigators
- Murat Bas, Dr., Principal investigator, Klinikum rechts der Isar, Hals-Nasen-Ohrenklinik, Ismaninger Str. 22 81675 München
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01154361
- Sponsor's protocol ID
- AMACE
- Status last verified
- Dec 2011
- First submitted
- 29 Jun 2010
- Last updated
- 23 Dec 2011
- Results posted
- No
Publications
Bas M, Greve J, Stelter K, Havel M, Strassen U, Rotter N, Veit J, Schossow B, Hapfelmeier A, Kehl V, Kojda G, Hoffmann TK. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015 Jan 29;372(5):418-25. doi: 10.1056/NEJMoa1312524.
PubMed 25629740
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Study, Randomized, Double-blind With 2 Groups as Prove of Concept for the Treatment of ACEI Induced Angioedema With Subcutaneous Icatibant
- ClinicalTrials.gov ID
- NCT01154361
- Acronym / sponsor ID
- AMACE
- Conditions
- Angioedema
- Keywords
- ACE inhibitor induced angioedema, Bradykinin, Non-itching edema, Non-allergic angioedema, Quincke edema, Drug induced angioedema, Bradykinin B2 receptor antagonist, Icatibant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- Technical University of MunichUniversity, hospital or other
- First posted
- 30 Jun 2010 (estimated)
- 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 a multicenter study recruiting patients with angioedema induced by ACEI.
Open-label treatment with subcutaneous Icatibant compared to a historic group of 47 patients with ACE inhibitor induced angioedema which the investigators have been previously treated in the investigators centers with current "standard" therapy (250 mg methylprednisolon and 2 mg clemastine).
In cases with fast progression of edema after application the study-drug, a second application with icatibant could be necessary. Rescue medication and intervention.
Detailed description
Sudden occurrence of subcutaneous or submucosal non-itchy swelling, so-called angioedema, is a well known side effect of angiotensin-converting enzyme inhibitors (ACEi), which may become life-threatening if the upper airway is involved. To be note, ACEi induced angioedema were always located in the head and neck region.
The pathophysiology of ACE inhibitor (ACEi) induced angioedema most likely resembles that of hereditary angioedema (HAE), i.e. it is mainly mediated by bradykinin induced activation of vascular bradykinin B2 receptors (BKR-2). In contrast to an increased bradykinin generation in HAE, treatment with ACEi decreases the bradykinin degradation in plasma and increases the biological activity of bradykinin.
The current pharmacotherapy of ACEi induced angioedema is not satisfactory. Antihistamines and corticosteroids may be effective in the treatment of urticaria with cutaneous edema and itchy, but are theoretically ineffective and hence superfluous in bradykinin induced angioedema. However, glucocorticoids still belong to the standard treatment of angioedema.
We hypothesized that the BKR-2 antagonist icatibant might be an effective therapy for ACEi-induced angioedema.
Patients with ACEi induced angioedema, located in the upper aero-digestive tract will be randomized and treated either with icatibant and plazebo or cortisone with clemastin and plazebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Icatibant (subcutaneous) and plazebo (intravenous) |
| Arm B | Active comparator | Drug: Cortisone + Clemastin (intravenous) and plazebo (subcutaneous) |
Who may qualify
- Ages
- 18 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age >= 18 <85 years
- Patient is currently treated with an ACEI
- Patient must have acute angioedema attack caused by an ACEI
- Treatment should be administrated within 10 hrs after onset by an ACEI
- Patient with angioedema of head and /or neck (face, lips, cheeks, tongue, soft palate/uvula, pharynx and larynx)
Key exclusion criteria (11 listed)
- Diagnosis of angioedema that was not caused by ACEI: e.g. hereditary angioedema (C1-INH deficiency), allergy, anaphylaxis, insect bite, trauma, infection, abscess, tumor, post-radiation or post-operative or processes related to salivary glands and others where it is unlikely that the ACEI is causing the angioedema
- Participation in a clinical trial of another investigational medicinal product (IMP) within 30 days
- Patients with acute urticaria
- Patients with a medical history of any angioedema before taking an ACEI
- Patients with an acute rash or hives in the face or somewhere else
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 |
|---|---|---|
| Icatibant (subcutaneous) and plazebo (intravenous) | Drug | Arm A |
| Cortisone + Clemastin (intravenous) and plazebo (subcutaneous) | Drug | Arm B |
Primary outcome
Time to complete resolution of angioedema
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 23 Dec 2011.
- Derived from this study: PubMed 25629740Bas M, Greve J, Stelter K, Havel M, Strassen U, Rotter N, Veit J, Schossow B, Hapfelmeier A, Kehl V, Kojda G, Hoffmann TK. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015 Jan 29;372(5):418-25. doi: 10.1056/NEJMoa1312524.
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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.
Murat Bas, Dr. principal investigator
Klinikum rechts der Isar, Hals-Nasen-Ohrenklinik, Ismaninger Str. 22 81675 München
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Icatibant (subcutaneous) and plazebo (intravenous) and Cortisone + Clemastin (intravenous) and plazebo (subcutaneous) in people with Angioedema, run by Technical University of Munich at 1 site in Germany.
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 7 inclusion and 11 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 23 Dec 2011. 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 Germany. 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.
What does this 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.
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?
Time to complete resolution of angioedema. 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 NCT01154361, 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 23 Dec 2011.