ACE Inhibitor-associated Angioedema
Conditions
Keywords
ACE inhibitor, Angioedema, Bradykinin, Swelling
Brief summary
Individuals with heart disease or high blood pressure are often prescribed angiotensin converting enzyme (ACE) inhibitors to treat their disease. However, the use of ACE inhibitors can be associated with angioedema, a rare but life-threatening condition that causes swelling of the face and other body parts. This study will evaluate the effectiveness of the drug HOE-140 at decreasing symptoms of angioedema in people taking ACE inhibitors who develop the condition.
Detailed description
People who take ACE inhibitors may develop angioedema, a condition that causes itchy and painful swelling beneath the skin around the eyes, lips, tongue, throat, hands, or feet. In severe cases, the throat may swell, obstructing the airway and leading to breathing difficulty. ACE inhibitors prevent the breakdown of a natural chemical in the body called bradykinin. Increased levels of bradykinin, which can cause swelling, may contribute to the development of angioedema. Blocking bradykinin receptor cells prevents bradykinin from initiating swelling and may lead to a possible decrease in angioedema symptoms. The purpose of this study is to evaluate the effectiveness of HOE-140, a bradykinin receptor blocker, at reducing symptoms in people with ACE inhibitor-associated angioedema. This study will enroll people admitted to the emergency room or hospital who have a severe case of ACE inhibitor-associated angioedema. Participants will be randomly assigned to receive an injection of either HOE-140 or placebo. Initially, participants will undergo an electrocardiogram to measure the electrical activity of the heart. Then blood pressure measurements, blood collection, a physical exam to determine the extent and duration of swelling, and photographs of the swelling will occur at 2, 4, 8, 16, and 24 hours following the start of treatment. Questionnaires will be completed by study staff and participants to assess changes in angioedema symptoms and the extent of swelling. Participants will remain in the hospital for 24 to 48 hours, depending on the severity of their symptoms. Blood will be collected at a follow-up visit that will occur 7 days after the resolution of angioedema symptoms.
Interventions
DRUGicatibant
Subcutaneous at time 0 and 6 hours
OTHERPlacebo
Subcutaneous at time 0 and 6 hours
Sponsors
Shire
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* The subject has ongoing angioedema while taking an ACE inhibitor. * The subject is between 18 and 80 years of age.
Exclusion criteria
* The subject has had angioedema while not taking an ACE inhibitor. * The subject's angioedema only involves the bowel. * The subject is known to be pregnant or has a positive urine pregnancy test. * The subject has started on an oral contraceptive within the last 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Resolution of Angioedema | 48 hours | Time interval between initiation of treatment and when there is no symptom, by visual analog scale \<1 cm. Data provided are for worst symptom. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Requirement for Intubation | T0 to T48 hours | — |
| Number of Participants Given Steroids | T0 to T48 hours | — |
| Number of Participants With Admission to Intensive Care Unit | T0 to T48 hours | — |
| Number of Participants Given Epinephrine | T0 to T48 hours | — |
| Systolic Blood Pressure | T0 to T48 hours | Average of blood pressure measurements from zero to forty-eight hours provided. |
| Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers | T0 to T48 hours | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Icatibant 30 mg icatibant will be administered subcutaneously 0 and 6 hours after randomization
icatibant: Subcutaneous at time 0 and 6 hours | 12 |
| Placebo Subcutaneous at time 0 and 6 hours
Placebo: Subcutaneous at time 0 and 6 hours | 18 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Missing primary endpoint data | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Icatibant |
|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 10.8 | 58.9 years STANDARD_DEVIATION 11.8 | 56.3 years STANDARD_DEVIATION 13.4 |
| Gender Female | 12 Participants | 19 Participants | 7 Participants |
| Gender Male | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 20 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 10 Participants | 3 Participants |
| Region of Enrollment United States | 18 Participants | 30 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 12 | 2 / 18 |
| serious Total, serious adverse events | 0 / 12 | 0 / 18 |
Outcome results
Primary
Time to Resolution of Angioedema
Time interval between initiation of treatment and when there is no symptom, by visual analog scale \<1 cm. Data provided are for worst symptom.
Time frame: 48 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Icatibant | Time to Resolution of Angioedema | 36 hours |
| Placebo | Time to Resolution of Angioedema | 24 hours |
Secondary
Number of Participants Given Epinephrine
Time frame: T0 to T48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Icatibant | Number of Participants Given Epinephrine | 0 Participants |
| Placebo | Number of Participants Given Epinephrine | 3 Participants |
Secondary
Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers
Time frame: T0 to T48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Icatibant | Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers | 11 Participants |
| Placebo | Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers | 16 Participants |
Secondary
Number of Participants Given Steroids
Time frame: T0 to T48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Icatibant | Number of Participants Given Steroids | 11 Participants |
| Placebo | Number of Participants Given Steroids | 16 Participants |
Secondary
Number of Participants With Admission to Intensive Care Unit
Time frame: T0 to T48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Icatibant | Number of Participants With Admission to Intensive Care Unit | 6 Participants |
| Placebo | Number of Participants With Admission to Intensive Care Unit | 6 Participants |
Secondary
Number of Participants With Requirement for Intubation
Time frame: T0 to T48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Icatibant | Number of Participants With Requirement for Intubation | 2 Participants |
| Placebo | Number of Participants With Requirement for Intubation | 1 Participants |
Secondary
Systolic Blood Pressure
Average of blood pressure measurements from zero to forty-eight hours provided.
Time frame: T0 to T48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Icatibant | Systolic Blood Pressure | 134 mmHg | Standard Deviation 13 |
| Placebo | Systolic Blood Pressure | 133 mmHg | Standard Deviation 17 |