Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema
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| ClinicalTrials.gov Identifier: NCT04679311 |
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Recruitment Status :
Recruiting
First Posted : December 22, 2020
Last Update Posted : February 22, 2022
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Sponsor:
Washington University School of Medicine
Information provided by (Responsible Party):
Washington University School of Medicine
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Angioedema Caused by Angiotensin-Converting-Enzyme Inhibitor | Biological: High ACE Activity Fresh Frozen Plasma Other: Normal Saline | Phase 2 |
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.
30 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, bradykinin, and substance P will be determined. The severity of angioedema will be assessed and serum levels of ACE activity, bradykinin and substance P will be determined at specific intervals after each subject is treated.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 30 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| 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. |
| Primary Purpose: | Treatment |
| Official Title: | High Angiotensin Converting Enzyme Activity-containing Plasma for the Treatment of Angiotensin Converting Enzyme Inhibitor-induced Angioedema |
| Actual Study Start Date : | December 22, 2020 |
| Estimated Primary Completion Date : | December 2023 |
| Estimated Study Completion Date : | December 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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
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Biological: 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 |
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Placebo Comparator: Normal Saline
Subjects will be treated with normal saline 500 cc.
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Other: Normal Saline
Subjects will be treated with normal saline 500 cc |
Primary Outcome Measures :
- Determine if treatment with 2 units of fresh frozen plasma that contains ≥ 50 U/L of ACE activity increases serum ACE activity [ Time Frame: 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 Outcome Measures :
- Determine how treatment affects the severity of angioedema using a published validated clinical rating scale [ Time Frame: 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
- The affect of treatment on bradykinin levels [ Time Frame: Compare bradykinin levels before treatment and at 30 minutes and 2 hours after treatment ]Determine how treatment affects bradykinin and substance P levels
- The affect of treatment on substance P levels [ Time Frame: Compare substance P levels before treatment and at 30 minutes and 2 hours after treatment ]Determine how treatment affects substance P levels
- Sustained change in serum ACE activity with treatment [ Time Frame: 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
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04679311
Contacts
| Contact: Steve J. Weintraub, M.D | 314-652-4100 ext 55298 | weintraub@wustl.edu | |
| Contact: Sara Chen, M.D. | 314-652-4100 | sara.chen2@va.gov |
Locations
| United States, Missouri | |
| Barnes-Jewish Hospital | Recruiting |
| Saint Louis, Missouri, United States, 63110 | |
| Contact: Steven J Weintraub, M.D. 314-652-4100 ext 55298 weintraub@wustl.edu | |
| Contact: Sara X Chen, M.D. sara.x.chen@gmail.com | |
Sponsors and Collaborators
Washington University School of Medicine
Investigators
| Principal Investigator: | Steven J Weintraub, M.D. | Washington University School of Medicine and the St. Louis VA Medical Center |
Publications:
| Responsible Party: | Washington University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT04679311 |
| Other Study ID Numbers: |
202002126 |
| First Posted: | December 22, 2020 Key Record Dates |
| Last Update Posted: | February 22, 2022 |
| Last Verified: | February 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Additional relevant MeSH terms:
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Angioedema Vascular Diseases Cardiovascular Diseases Urticaria Skin Diseases, Vascular |
Skin Diseases Hypersensitivity, Immediate Hypersensitivity Immune System Diseases |