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Effectiveness of Bradykinin Receptor Blocker at Reducing Swelling Associated With Angiotensin Converting Enzyme (ACE) Inhibitor-Associated Angioedema

This study is currently recruiting participants.
Verified by National Heart, Lung, and Blood Institute (NHLBI), August 2008

Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)
Information provided by: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00517582
  Purpose

Individuals with heart disease or high blood pressure are often prescribed angiotensin converting enzyme (ACE) inhibitors to treat their disease. However, the use of ACE inhibitors can be associated with angioedema, a rare but life-threatening condition that causes swelling of the face and other body parts. This study will evaluate the effectiveness of the drug HOE-140 at decreasing symptoms of angioedema in people taking ACE inhibitors who develop the condition.


Condition Intervention Phase
Angioneurotic Edema
Drug: HOE-140
Other: Placebo
Phase I

MedlinePlus related topics:   Edema   

ChemIDplus related topics:   Icatibant    Icatibant acetate   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:   Study of a Bradykinin Receptor Blocker in Angiotensin Converting Enzyme Inhibitor-Associated Angioedema

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Time to resolution of angioedema, as defined as the time interval between when the participant first noted the onset of symptoms and when there is no objective evidence of angioedema by physical examination [ Time Frame: Measured at follow-up visit 7 days following resolution of angioedema ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Length of hospital stay, admission to the intensive care unit, requirement for intubation, duration of intubation, use of steroids, use of histamine receptor type 1 (H1) and H2 blockers, use of epinephrine, and blood pressure levels [ Time Frame: Measured at follow-up visit 7 days following resolution of angioedema ] [ Designated as safety issue: No ]

Estimated Enrollment:   24
Study Start Date:   September 2007
Estimated Study Completion Date:   December 2009
Estimated Primary Completion Date:   December 2009 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
HOE-140: Experimental Drug: HOE-140
Subcutaneous at time 0 and 6 hours
Placebo: Placebo Comparator Other: Placebo
Subcutaneous at time 0 and 6 hours

Detailed Description:

People who take ACE inhibitors may develop angioedema, a condition that causes itchy and painful swelling beneath the skin around the eyes, lips, tongue, throat, hands, or feet. In severe cases, the throat may swell, obstructing the airway and leading to breathing difficulty. ACE inhibitors prevent the breakdown of a natural chemical in the body called bradykinin. Increased levels of bradykinin, which can cause swelling, may contribute to the development of angioedema. Blocking bradykinin receptor cells prevents bradykinin from initiating swelling and may lead to a possible decrease in angioedema symptoms. The purpose of this study is to evaluate the effectiveness of HOE-140, a bradykinin receptor blocker, at reducing symptoms in people with ACE inhibitor-associated angioedema.

This study will enroll people admitted to the emergency room or hospital who have a severe case of ACE inhibitor-associated angioedema. Participants will be randomly assigned to receive an injection of either HOE-140 or placebo. Initially, participants will undergo an electrocardiogram to measure the electrical activity of the heart. Then blood pressure measurements, blood collection, a physical exam to determine the extent and duration of swelling, and photographs of the swelling will occur at 2, 4, 8, 16, and 24 hours following the start of treatment. Questionnaires will be completed by study staff and participants to assess changes in angioedema symptoms and the extent of swelling. Participants will remain in the hospital for 24 to 48 hours, depending on the severity of their symptoms. Blood will be collected at a follow-up visit that will occur 7 days after the resolution of angioedema symptoms.

  Eligibility
Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

Inclusion Criteria:

  • Ambulatory
  • ACE inhibitor-associated angioedema, as defined as swelling of the lips, pharynx, or face while taking an ACE inhibitor, no history of angioedema while not taking an ACE inhibitor, and no evidence of abnormal C1 inhibitor concentration or abnormal complement levels. People with possible cases of ACE inhibitor-associated bowel edema will not be enrolled.
  • If female, must be postmenopausal for at least 1 year prior to study entry, undergone surgical sterilization, or willing to use an effective form of birth control and take a pregnancy test daily for the duration of the study

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Started taking birth control pills in the 6 months prior to study entry
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00517582

Contacts
Contact: Nancy J. Brown, MD     615-343-8701     nancy.j.brown@vanderbilt.edu    

Locations
United States, Tennessee
Vanderbilt University Medical Center     Recruiting
      Nashville, Tennessee, United States, 37205
      Contact: Nancy J Brown, MD     615-343-8701        
      Contact: Libby Stone, RN     615-343-8701        

Sponsors and Collaborators

Investigators
Principal Investigator:     Nancy J. Brown, MD     Vanderbilt University    
  More Information


Responsible Party:   Vanderbilt University Medical Center ( Nancy J. Brown, MD )
Study ID Numbers:   495, HL079184-Specific Aim 1
First Received:   August 15, 2007
Last Updated:   August 29, 2008
ClinicalTrials.gov Identifier:   NCT00517582
Health Authority:   United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
ACE Inhibitor  
Angioedema  
Bradykinin  
Swelling  

Study placed in the following topic categories:
Hypersensitivity
Bradykinin
Skin Diseases
Angioedema
Hypersensitivity, Immediate
Vascular Diseases
Edema
Urticaria
Icatibant

Additional relevant MeSH terms:
Vasodilator Agents
Skin Diseases, Vascular
Immune System Diseases
Therapeutic Uses
Cardiovascular Diseases
Cardiovascular Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 07, 2008




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