Efficacy of a new intravenous β2-adrenergic agonist (bedoradrine, MN-221) for patients with an acute exacerbation of asthma.
BACKGROUND
Many patients with acute exacerbation of asthma are non-responders to inhaled β-adrenergic agonists. The goal of this study was to evaluate the safety and efficacy of intravenous bedoradrine (MN-221), a highly selective β2-adrenergic agonist, as adjunct to standard therapy in the management of patients with acute exacerbation of asthma who did not respond to standard therapy.


METHODS
Patients (N = 167) received standard therapy and were randomized to either bedoradrine (1200 μg) or placebo. Safety and efficacy parameters were monitored hourly for 3 h, followed by a 24-h follow-up visit and an 8-day follow-up phone call. Change in %FEV1 from baseline to Hour 3 was the primary outcome. Secondary outcome measures included change in %FEV1 at 1 and 2 h, change in dyspnea score at 1, 2, and 3 h, treatment failure rate, defined as a combination of hospitalization on the index visit or return to the emergency department within 1 week, and safety monitoring.


RESULTS
There was no significant difference in %FEV1 at 3 h between the 2 groups. The dyspnea scores were significantly improved for patients treated with bedoradrine compared to placebo (AUC0-2 hP < 0.005, AUC0-3 hP < 0.05). The safety profile for those treated with bedoradrine was consistent with the known mechanism of action of β-adrenergic agonists, and included both cardiovascular and metabolic effects.


CONCLUSIONS
Intravenous bedoradrine, in addition to standard therapy, did not significantly increase %FEV1 at 3 h, but it was associated with significantly improved dyspnea scores.


BACKGROUND
Clinicaltrials.gov; study name: MN-221-CL-007, registration number: NCT00838591; www.clinical trials.gov.
Division of Emergency Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. Electronic address: houses@wustl.edu.
Stacey L
SL
House
MediciNova, Inc., San Diego, CA, USA.
Kazuko
K
Matsuda
MediciNova, Inc., San Diego, CA, USA.
Geoffrey
G
O'Brien
MediciNova, Inc., San Diego, CA, USA.
Malath
M
Makhay
MediciNova, Inc., San Diego, CA, USA.
Yuichi
Y
Iwaki
Division of Emergency Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Ian
I
Ferguson
Olive View-UCLA Medical Center, Sylmar, CA, USA.
Luis M
LM
Lovato
Division of Emergency Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Lawrence M
LM
Lewis
D000081:Acetamides / Q000008:administration & dosage* / Q000009:adverse effects; D000208:Acute Disease; D000280:Administration, Inhalation; D061605:Administration, Intravenous; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000208:ethnology; D001993:Bronchodilator Agents / Q000008:administration & dosage; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage* / Q000009:adverse effects; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D013147:Spirometry; D016896:Treatment Outcome
D000081:Acetamides; D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D009281:Naphthalenes; C425888:bedoradrine; D009241:Ipratropium; D011241:Prednisone
Asthma; Beta agonists; Emergency medicine; Pharmacotherapy