Prematta et al randomly assigned to receive C1-INH or placebo infusion every 3 days in two different 17-day treatment periods to evaluate for a difference in the frequency of acute attacks. Disease activity was reduced 60% during the C1-INH treatment period compared with the placebo treatment period. Also from that publication was a study on acute HAE attacks in which patients were randomly assigned to receive C1-INH concentrate versus placebo for acute treatment. Patients treated with C1-INH showed a signiﬁcantly shorter mean time from infusion to the initial signs of improvement of symptoms (55 minutes versus 563 minutes). Moreover, 38 of 55 attacks (69%) treated with C1-INH concentrate had some improvement within 30 minutes of infusion compared with 1 of 49 (2%) attacks in the placebo group. Patients had no serious short-term side effects from receiving C1-INH and were monitored for up to 4 years without anyone developing HIV, hepatitis B, or hepatitis C. Another randomized, double-blind, placebo-controlled trial was conducted by Kunschak et al (1998). They compared 11 patients treated for acute HAE attacks with 25 U/kg body weight of C1 INH (60 total treatments) with 11 patients treated with placebo for acute HAE attacks (57 total treat- ments). The mean time from infusion to the earliest sign of symptom relief was signiﬁcantly shorter in patients given C1-INH concentrate compared with placebo. The mean time from infusion to complete resolution of symptoms was also signiﬁcantly shorter in the treatment group: 23.98 hours in the treatment group compared with 34.98 hours in the placebo group. However, because the placebo data included 49 of the 57 treatments that required open-label C1-INH as rescue therapy, the difference between these two groups is probably underestimated. Kunschak et al also studied the half-life of C1-INH by investigating both functional and antigenic C1-INH levels. They found that the mean functional C1-INH half-life was 38.87 ± 19.75 hours, and the mean antigenetic C1-INH half-life was 24.01 ± 9.70 hours. They also noted that serum C4 concentrations remained elevated much longer than C1-INH levels – staying at peak levels at least 24 hours post C1-INH infusion. They also reviewed the viral safety of C1-INH concentrate and found that of the 22 patients receiving a total of 157 C1-INH concentrate infusions, there was no evidence of viral infections. Only minor adverse reac- tions related to C1-INH were reported and included 1 patient with nausea and bad aftertaste, 1 patient with shortness of breath, and 1 patient with dizziness and headache. As stated previously, C1-INH concentrate has been available for HAE treatment for many years in parts of Europe and several groups have published their personal results for 978 the treatment of acute HAE attacks with C1-INH. Bork and Barnstedt (2001) compiled data from HAE patients in Germany who received C1-INH concentrate for laryngeal edema and compared the length of attacks with patients who had laryngeal edema in the past, but did not receive C1-INH concentrate. The study was not double-blinded or placebo-controlled as everyone was treated with C1-INH concentrate when it was available. The group treated 18 patients for a total of 193 epi- sodes of laryngeal edema with 500–1000 U of C1-INH. Most of the patients treated with C1-INH had some improvement of symptoms within 1 hour with a mean time of 42.2 minutes. The group found that the patients treated with C1-INH concentrate for symptoms of laryngeal edema had an average duration of symptoms of 15.3 ± 9.3 hours which was signiﬁcantly shorter than patients who did not receive C1-INH concentrate and had a mean duration of symptoms of 100.8 ± 26.2 hours. Bork et al (2005) retrospectively examined acute abdominal attacks of HAE and compared 75 patients with 17,444 untreated acute abdominal attacks to 4,834 acute abdominal attacks treated with C1-INH concentrate (Bork et al 2005). The usual dose of C1-INH concentrate was 500 U; however, higher doses were given if a clinical response was not achieved, or if the patient’s weight was over 80 kg, then they were treated with 1000 U of C1-INH concentrate. The mean duration of an acute abdominal attack was signiﬁcantly shorter at 30.3 ± 23.2 hours when treated with C1-INH con- centrate compared with 93.8 ± 42.7 hours when patients were not treated for their attacks. However, the group also noted that C1-INH concentrate seemed to have a more dramatic effect on an acute attack if given early in the course of the attack. Patients often needed a larger amount of C1-INH if they were treated later for their acute attack. Bork et al noted that the mean time from injection to initial improvement of symptoms varied depending on the timing of infusion; 53.5 minutes if C1-INH concentrate was given within 2 hours of the onset of an attack compared with 114 minutes if C1-INH was given greater than 2 hours after the onset of symptoms. This group also examined the safety of C1-INH concentrate in these patients. They reported no HIV, hepatitis B, or hepatitis C transmission after C1-INH concentrate administration. The only adverse effects were faintness, vertigo, headaches, reddened face, feeling of warmth or coldness, paresthesias, coldness, fevers, and chills in a small group of patients. All of the patients who had some side effects were reportedly able to receive subsequent infusions and had fewer side effects with additional treatments. Farkas et al (2007) reviewed a group of patients treated for HAE with C1-INH from 1996 to 2006. The patients, Therapeutics and Clinical Risk Management 2008:4(5)