|Author, date and country||Patient group||Study type (level of evidence)||Outcomes||Key results||Study Weaknesses|
|Cicardi et al,|
|56 known adult HAE patients (type I and II) in the For Angioedema Subcutaneous Treatment (FAST-1) trial (USA).|
Eenrolled for treatment within 6 hours of onset with moderate to severe HAE attack and received either icatibant (27 patients) or placebo (29 patients)
74 known adult HAE patients (type I and II) for FAST-2 trial (Europe) for treatment within 6 hours of onset with moderate to severe HAE attack and received either icatibant (36 patients) 30gm once subcutaneously or oral tranexamic acid (38 patients) 3g daily for 2 days
Exclusion criteria: <18 years of age, diagnosis of angioedema other than HAE, serious concomitant illness, pregnancy or lactation, received analgesia for current attack.
Outcomes assessed by both patients and study investigators
|Level 2b – data from two multi-centre prospective randomised double-blind phase 3 trials.||Primary – median time required for relief of the most severe symptom||FAST-1 trial Primary end point reached in 2.5hrs with icatibant vs 4.6hrs with placebo (P=0.14)|
FAST-2 trial Primary end point reached in 2.0hrs with icatibant vs 12.0hrs with tranexamic acid (P=<0.001)
|Small samples with risk of underpower in FAST-1 trial|
Comparison with oral tranexamic acid may be flawed as it is not the ‘gold standard’ treatment for acute exacerbation of hereditary angioedema. This may be hampered by the centres being in different parts of the world where ‘gold standard’ treatment differs (eg. Europe vs USA)
Of those initially screened, some of those were enrolled for each of the two trials but slightly less was assigned treatment. There was no mention of what happened or why those enrolled did not get randomised and no mention of drop-out rates of those who were assigned treatment.
Measurements are subjective according to each patient and investigator.
Both trials designed and funded by Jerini (German manufacturer of Icatibant seeking FDA approval). Assistance with medical writing by Carl V. Felton at Prime Healthcare supported by Jerini.
|Secondary – median time required for relief of all symptoms||FAST-1 Trial Secondary end point reached in 8.5hrs with icatibant vs 19.4hrs with placebo (P=0.08)|
FAST-2 Secondary end point reached in 10.0hrs with icatibant vs 51.0hrs with tranexamic acid (P=<0.001
|Rescue medication||In FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication (C1 esterase inhibitor concentrate, antiemetic agents or opiates) within the first 12hrs|
In FAST-2 study, 0 recipients of icatibant and 5 recipients of tranexamic acid needed treatment with rescue medication within the first 12hrs
No icatibant-related serious adverse events were reported