ACE Inhibitor Induced Angioedema
Conditions
Brief summary
A double-blind, randomized, controlled trial comparing the safety and effectiveness of conventional therapy with ecallantide to conventional therapy with placebo.
Interventions
DRUGecallantide 60 mg
Administered as two 3 mL SC injections, each containing 30 mg ecallantide
DRUGecallantide 30 mg
Administered as one 3 mL SC injection containing 30 mg ecallantide
DRUGecallantide 10 mg
Administered as one 3 mL SC injection containing 10 mg ecallantide.
DRUGplacebo
Administered as two SC 3 mL injections
DRUGplacebo match for 30 mg ecallantide arm
One 3 mL SC injection of matching placebo given to subjects randomized to the 30 mg ecallantide arm.
DRUGplacebo match for 10 mg ecallantide arm
One 3 mL SC injection of matching placebo given to subjects randomized to the 10 mg ecallantide arm.
Sponsors
Shire
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females 18 years of age or older * Must currently be on ACE inhibitor therapy and have received a dose within 36 hours * Presenting with ACEIA of the head/neck region within 12 hours after onset * All females must have a negative urine pregnancy test prior to administration of the study drug. Those who have had a total hysterectomy, bilateral oophorectomy or are two years post-menopausal do not require a pregnancy test.
Exclusion criteria
* Hypersensitivity to ecallantide * Pregnancy or breast feeding * Patients who have had angioedema and were not concurrently on an ACE inhibitor * Patients exhibiting urticaria * Patients who are intubated or who have a tracheostomy related to the current episode of angioedema * Opinion of the investigator that the patient would not be a good candidate * Participation in another investigational study within 30 days prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Efficacy of Ecallantide | 6 hours | Compare the proportion of patients meeting prespecified discharge criteria in the group receiving ecallantide with conventional therapy to patients receiving placebo with conventional therapy. Patients were evaluated against 6 discharge eligibility criteria at 1,2,3,4,5, and 6 hours after study drug administration or until discharged from the ER. A responder was defined as a patient meeting all six discharge eligibility criteria as below: • Improvement of edema to a little better or a lot better as assessed by health care provider using a five point scale • Stable vital signs (within an acceptable range) • Absence of stridor • Absence of dyspnea or use of accessory muscles during respiration • Absence of drooling • Able to drink without difficulty |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Symptom Resolution Based on the Visual Analog Scale (VAS) | 6 hours | Compare the time to onset of symptom resolution between the ecallantide-treated and placebo-treated groups. The patient assessed severity of the angioedema attack using a VAS at baseline and following study drug administration every 15 minutes for the first 2 hours and then every 30 minutes through 6 hours post dosing or until the time of discharge from the ER (whichever occurred first). The scale ranged from totally resolved to very severe. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ecallantide 10 mg | 20 |
| Ecallantide 30 mg | 19 |
| Ecallantide 60 mg | 19 |
| Placebo | 18 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Study Terminated | 1 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Ecallantide 10 mg | Ecallantide 30 mg | Ecallantide 60 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 5 Participants | 6 Participants | 6 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 14 Participants | 13 Participants | 12 Participants | 54 Participants |
| Region of Enrollment United States | 20 Participants | 19 Participants | 19 Participants | 18 Participants | 76 Participants |
| Sex: Female, Male Female | 13 Participants | 8 Participants | 9 Participants | 11 Participants | 41 Participants |
| Sex: Female, Male Male | 7 Participants | 11 Participants | 10 Participants | 7 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 20 | 11 / 19 | 12 / 19 | 8 / 18 |
| serious Total, serious adverse events | 6 / 20 | 8 / 19 | 8 / 19 | 5 / 18 |
Outcome results
Primary
Safety and Efficacy of Ecallantide
Compare the proportion of patients meeting prespecified discharge criteria in the group receiving ecallantide with conventional therapy to patients receiving placebo with conventional therapy. Patients were evaluated against 6 discharge eligibility criteria at 1,2,3,4,5, and 6 hours after study drug administration or until discharged from the ER. A responder was defined as a patient meeting all six discharge eligibility criteria as below: • Improvement of edema to a little better or a lot better as assessed by health care provider using a five point scale • Stable vital signs (within an acceptable range) • Absence of stridor • Absence of dyspnea or use of accessory muscles during respiration • Absence of drooling • Able to drink without difficulty
Time frame: 6 hours
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Safety and Efficacy of Ecallantide | 13 participants |
| Ecallantide 10 mg | Safety and Efficacy of Ecallantide | 17 participants |
| Ecallantide 30 mg | Safety and Efficacy of Ecallantide | 17 participants |
| Ecallantide 60 mg | Safety and Efficacy of Ecallantide | 17 participants |
Secondary
Time to Symptom Resolution Based on the Visual Analog Scale (VAS)
Compare the time to onset of symptom resolution between the ecallantide-treated and placebo-treated groups. The patient assessed severity of the angioedema attack using a VAS at baseline and following study drug administration every 15 minutes for the first 2 hours and then every 30 minutes through 6 hours post dosing or until the time of discharge from the ER (whichever occurred first). The scale ranged from totally resolved to very severe.
Time frame: 6 hours
Population: Time to Symptom Resolution Based on the VAS (Safety Population)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Symptom Resolution Based on the Visual Analog Scale (VAS) | 0.50 hours |
| Ecallantide 10 mg | Time to Symptom Resolution Based on the Visual Analog Scale (VAS) | 0.30 hours |
| Ecallantide 30 mg | Time to Symptom Resolution Based on the Visual Analog Scale (VAS) | 0.27 hours |
| Ecallantide 60 mg | Time to Symptom Resolution Based on the Visual Analog Scale (VAS) | 0.50 hours |