Blinded Safety & Efficacy Placebo Controlled Study of Icatibant for Angiotensin Converting Enzyme Inhibitor Induced Angioedema

NCT ID: NCT01919801

Last Updated: 2021-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-02
• Study Completion Date: 2015-08-22

Brief Summary

This study is being conducted to compare the safety and efficacy of icatibant with placebo in the treatment for Angiotensin-Converting Enzyme Inhibitor (ACE-I)-Induced Angioedema in Adults.

Detailed Description

Angiotensin-converting enzyme inhibitors (ACE-Is) are the class of medications prescribed most frequently for the treatment of hypertension. They are also used post myocardial infarction as well as in patients with heart failure, diabetes mellitus, and chronic kidney disease. Approximately 35 to 40 million patients are on ACE-Is worldwide.

Study HGT-FIR-096 is a multicenter, Phase III, randomized, double-blind, two-armed, placebo-controlled trial. The study population will consist of 118 adult patients, 18 years of age or older, who present with an acute ACE-I-induced angioedema attack. The primary aim of the study is to demonstrate that icatibant is significantly more effective than placebo in resolving attacks of angioedema caused by ACE-I based on the Time to Meeting Discharge Criteria (TMDC). Safety and tolerability, as well as the pharmacokinetics (PK), of icatibant will also be evaluated. Eligible patients will be randomized at a 1:1 ratio to receive a single sub-cutaneous injection of either 30 mg icatibant or placebo.

Conditions

Angiotensin Converting Enzyme Inhibitor Induced Angioedema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Icatibant

Icatibant at a dose of 30 mg will be administered as a single subcutaneous injection

Group Type: EXPERIMENTAL

Icatibant

Intervention Type: DRUG

Single dose of 30 mg icatibant administered within 12 hours of the onset of an acute attack of ACE-I-induced angioedema

Placebo

Placebo will be administered as a single subcutaneous injection

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Icatibant

Single dose of 30 mg icatibant administered within 12 hours of the onset of an acute attack of ACE-I-induced angioedema

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Firazyr

Eligibility Criteria

Inclusion Criteria

1. Male or female, 18 years of age or older.

2. Patient is currently being treated with an ACE inhibitor.

3. Patient presenting with an ACE inhibitor-induced angioedema attack of the head and/or neck region within 12 hours of onset (must be sufficiently less than 12 hours to allow study drug to be given with 12 hours of attack onset).

4. Angioedema must be considered at least moderate in severity for at least one of the four angioedema-associated airway symptoms (difficulty breathing, difficulty swallowing, voice changes, tongue swelling).

5. Patient must have voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient.

6. Females must have a negative urine pregnancy test prior to administration of the study medication, with the exception of those females who have had a total hysterectomy or bilateral oophorectomy, or who are 2 years post-menopausal.

Exclusion Criteria

1. Patient has a diagnosis of angioedema of other etiology (eg, hereditary or acquired angioedema, allergic angioedema [eg, food, insect bite or sting, evident clinical response to antihistamines and/or corticosteroids], anaphylaxis, trauma, abscess or infection or associated disease, local inflammation, local tumor, post-operative or post-radiogenic edema, salivary gland disorders, other [non-ACE inhibitor] drug-induced angioedema).

2. Patients with a family history of recurrent angioedema.

3. Patients who have had a previous episode(s) of angioedema while not on ACE inhibitor therapy.

4. Patients with acute urticaria (itchy, erythematous wheals).

5. Patients who have an intervention to support the airway (eg, intubation, tracheotomy, cricothyrotomy) due to the current attack of angioedema.

6. Patient has any of the following vascular conditions that, in the judgment of the investigator, would be a contraindication to participation in the study.

• Unstable angina pectoris or acute myocardial ischemia
• Hypertensive urgency or emergency (diastolic blood pressure [DBP] >120 mm Hg or systolic blood pressure [SBP] >180 mm Hg)
• Within 1 month of a stroke or transient ischemic attack
• New York Heart Association (NYHA) heart failure class IV

7. Patient has a serious or acute condition or illness that, in the judgment of the investigator, would interfere with evaluating the safety and/or efficacy assessments of the study (eg, a condition or illness requiring hemodialysis).

8. Patient is pregnant or breast feeding.

9. Patient has participated in another investigational study in the past 30 days.

10. Patient is unable to understand the nature, scope, and possible consequences of the protocol, or is unlikely or unable to comply with the protocol assessments, or is unlikely to complete the study for any reason.

11. Patients who are not suitable for the study in the opinion of the investigator.

12. Patient has experienced hypersensitivity to the active substance of the investigational product or to any of its excipients.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PPD Development, LP

INDUSTRY

Sponsor Role: collaborator

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Detroit Receiving Hospital and University Health Center

Detroit, Michigan, United States

Sinai Grace Hospital

Detroit, Michigan, United States

Henry Ford Health System

Detroit, Michigan, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

William Beaumont Hospital

Troy, Michigan, United States

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Barnes Jewish Hospital

St Louis, Missouri, United States

Washington University

St Louis, Missouri, United States

Inspira Health Network

Vineland, New Jersey, United States

University of New Mexico

Albuquerque, New Mexico, United States

Kings County Hospital Center

Brooklyn, New York, United States

SUNY Downstate Medical Center

Brooklyn, New York, United States

Weill Medical College of Cornell University

New York, New York, United States

University of California San Diego Medical Center

La Jolla, California, United States

University of California San Diego

La Jolla, California, United States

Washington Hospital Center

Washington D.C., District of Columbia, United States

UF Health Shands Hospital

Gainesville, Florida, United States

Orlando Health

Orlando, Florida, United States

Tampa General Hospital

Tampa, Florida, United States

Federal Health Care Center

Chicago, Illinois, United States

Cook County Hospital

Chicago, Illinois, United States

University of Kansas Cancer Center

Kansas City, Kansas, United States

Ochsner Medical Center

New Orleans, Louisiana, United States

University of Maryland School of Medicine

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Womens Hospital

Boston, Massachusetts, United States

Baystate Medical Center

Springfield, Massachusetts, United States

East Carolina University

Greenville, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University Hospital - East

Gahanna, Ohio, United States

Summit Health

Chambersburg, Pennsylvania, United States

Hahnemann University Hospital

Philadelphia, Pennsylvania, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

University of South Carolina School of Medicine

Columbia, South Carolina, United States

Baylor University Medical Center

Dallas, Texas, United States

John Peter Smith Hospital

Fort Worth, Texas, United States

University of Texas Medical Branch

Galveston, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, Canada

Kingston General Hospital

Kingston, Ontario, Canada

Hotel Dieu Hospital

Kingston, Ontario, Canada

Soroka University Medical Center

Beersheba, , Israel

Bnai Zion Medical Center

Haifa, , Israel

Ziv Medical Center

Safed, , Israel

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Brighton and Sussex University Hospitals NHS Trust

Brighton, , United Kingdom

Royal Devon and Exeter Hospital NHS Trust

Exeter, , United Kingdom

University Hospital Aintree

Liverpool, , United Kingdom

Manchester Royal Infirmary

Manchester, , United Kingdom

Queen's Medical Centre

Nottingham, , United Kingdom

Countries

United States; Canada; Israel; United Kingdom

References

Sinert R, Levy P, Bernstein JA, Body R, Sivilotti MLA, Moellman J, Schranz J, Baptista J, Kimura A, Nothaft W; CAMEO study group. Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1402-1409.e3. doi: 10.1016/j.jaip.2017.03.003. Epub 2017 May 25.

Reference Type: RESULT

PMID: 28552382 (View on PubMed)

Other Identifiers

2014-001213-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HGT-FIR-096

Identifier Type: -

Identifier Source: org_study_id