Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor
Conditions
Brief summary
Angiotensin Converting Enzyme (ACE) inhibitors are among the most important and widely prescribed drugs. They reduce the morbidity and mortality associated with high blood pressure, heart disease, and kidney disease. Unfortunately, their use carries the risk of causing life-threatening airway swelling in some patients. There is currently no treatment for this condition. A novel treatment approach that may reduce or completely reverse the swelling will be tested.
Detailed description
The investigators will test the hypothesis that treatment with fresh frozen plasma that contains high levels of ACE activity will increase serum ACE activity and thereby cause the degradation of mediators of ACE inhibitor-induced angioedema, such as bradykinin and substance P, resulting in a shortening of the course of ACE inhibitor-induced angioedema. 16 patients with ACE inhibitor-induced angioedema will be randomized 1:1 to treatment with either 2 units of fresh frozen plasma that has been preselected for high ACE activity content (≥50 U/L) or an equal volume of normal saline. A baseline assessment of the severity of the angioedema will be performed and baseline serum levels of ACE activity will be determined. The severity of angioedema will be assessed and serum levels of ACE activity will be determined at specific intervals after each subject is treated.
Interventions
BIOLOGICALHigh ACE Activity Fresh Frozen Plasma
Subjects will be treated with fresh frozen plasma that has been preselected for ACE activity content of ≥ 50 U/L
OTHERNormal Saline
Subjects will be treated with normal saline 500 cc
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The laboratory that performs the assays and the assessor of the angioedema will be blinded to the treatment the subject received.
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 moderate to severe angioedema affecting the upper aerodigestive tract (face, lips, cheeks, tongue, soft palate/uvula, pharynx, and larynx). The severity of the angioedema attack will be determined by the subject's worst severity rating at baseline among 4 clinical domains (difficulty breathing, difficulty swallowing, voice changes, and tongue swelling) based on a clinically validated angioedema severity scale29 (Table) * Presenting with ACE inhibitor-induced angioedema within 12 hours after onset * All females must have a locally obtained negative 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. * Must be able to provide written informed consent to participate in the study to fulfill all study requirements
Exclusion criteria
* Pregnancy and/or breast feeding * Patients with angioedema that is likely due to causes other than ACE inhibitors, including hereditary angioedema, acquired angioedema, and allergic angioedema (food, insect bite or sting with clear response to anti-allergy medications) * Patients exhibiting acute urticaria * Evident clinical response to glucocorticoids, antihistamines, or epinephrine * A family history of recurrent angioedema * Documented intolerance to plasma * Documented congenital deficiency of immunoglobulin A in the presence of anti-immunoglobulin A antibodies * Patients with heart failure of the severity that precludes safe transfusion of High ACE activity plasma * Patients with acute pulmonary edema * Patients with morbid obesity as defined by BMI\>40; morbidly obese patients have a higher volume of blood needing higher amounts of plasma and therefore will be excluded from this pilot study * Opinion of the investigator that the patient would not be a good candidate * Participation in a clinical study in the past 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine if Treatment With 2 Units of Fresh Frozen Plasma That Contains ≥ 50 U/L of ACE Activity Increases Serum ACE Activity | Compare serum ACE activity before treatment and 30 minutes after treatment | The subjects' serum ACE activity will be assessed prior to treatment and 30 minutes after treatment and compared to determine if the treatment increases serum ACE activity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine How Treatment Affects the Severity of Angioedema Using a Published Validated Clinical Rating Scale | Compare angioedema severity before treatment and 30 minutes, 2 hours, and 8 hours after treatment | The severity of the the subjects' angioedema will be assessed using a published validated clinical rating scale before treatment and at 30 minutes, 2 hours, and 8 hours after treatment |
| Sustained Change in Serum ACE Activity With Treatment | Compare serum ACE activity before treatment and at 2 hours and 8 hours after treatment | Determine if treatment results in a sustained change in ACE activity levels |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High ACE Activity Fresh Frozen Plasma Subjects will be treated with 2 units of fresh frozen plasma that have been preselected to contain ACE activity ≥50 U/L
High ACE Activity Fresh Frozen Plasma: Subjects will be treated with fresh frozen plasma that has been preselected for ACE activity content of ≥ 50 U/L | 0 |
| Normal Saline Subjects will be treated with normal saline 500 cc.
Normal Saline: Subjects will be treated with normal saline 500 cc | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Normal Saline | Total | High ACE Activity Fresh Frozen Plasma |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 0 Participants |
| Age, Continuous | 47.9 years | 47.9 years | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | — |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | — |
| Region of Enrollment United States | 2 participants | 2 participants | — |
| Sex: Female, Male Female | 1 Participants | 1 Participants | — |
| Sex: Female, Male Male | 1 Participants | 1 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 2 |
| other Total, other adverse events | 0 / 0 | 0 / 2 |
| serious Total, serious adverse events | 0 / 0 | 0 / 2 |
Outcome results
Primary
Determine if Treatment With 2 Units of Fresh Frozen Plasma That Contains ≥ 50 U/L of ACE Activity Increases Serum ACE Activity
The subjects' serum ACE activity will be assessed prior to treatment and 30 minutes after treatment and compared to determine if the treatment increases serum ACE activity
Time frame: Compare serum ACE activity before treatment and 30 minutes after treatment
Population: Blood was never drawn due to pandemic related issues, the subjects' serum ACE activity were not assessed/drawn prior to treatment and nor 30 minutes after treatment, no result data available.
Secondary
Determine How Treatment Affects the Severity of Angioedema Using a Published Validated Clinical Rating Scale
The severity of the the subjects' angioedema will be assessed using a published validated clinical rating scale before treatment and at 30 minutes, 2 hours, and 8 hours after treatment
Time frame: Compare angioedema severity before treatment and 30 minutes, 2 hours, and 8 hours after treatment
Population: Due to pandemic related issues, no data was collected. Clinical rating scale was never done.
Secondary
Sustained Change in Serum ACE Activity With Treatment
Determine if treatment results in a sustained change in ACE activity levels
Time frame: Compare serum ACE activity before treatment and at 2 hours and 8 hours after treatment
Population: Due to pandemic related issues,sustained change in serum ACE activity with treatment was never collected.