Clinical trial NCT04679311: Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema
Official title: High Angiotensin Converting Enzyme Activity-containing Plasma for the Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2020-12-22
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Determine if Treatment With 2 Units of Fresh Frozen Plasma That Contains ≥ 50 U/L of ACE Activity Increases Serum ACE Activity
timeFrame: Compare serum ACE activity before treatment and 30 minutes after treatment
Secondary outcomes:
measure: Determine How Treatment Affects the Severity of Angioedema Using a Published Validated Clinical Rating Scale
timeFrame: Compare angioedema severity before treatment and 30 minutes, 2 hours, and 8 hours after treatment
measure: Sustained Change in Serum ACE Activity With Treatment
timeFrame: Compare serum ACE activity before treatment and at 2 hours and 8 hours after treatment
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
Study officials:
affiliation: Washington University School of Medicine and the St. Louis VA Medical Center
name: Steven J Weintraub, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen SX, Hermelin D, Weintraub SJ. Possible donor-dependent differences in efficacy of fresh frozen plasma for treatment of ACE inhibitor-induced angioedema. J Allergy Clin Immunol Pract. 2019 Jul-Aug;7(6):2087-2088. doi: 10.1016/j.jaip.2019.02.027. Epub 2019 Mar 2. No abstract available.