Safety of intramuscular influenza vaccine in patients receiving oral anticoagulation therapy: a single blinded multi-centre randomized controlled clinical trial

BACKGROUND Influenza vaccines are recommended for administration by the intramuscular route. However, many physicians use the subcutaneous route for patients receiving an oral anticoagulant because this route is thought to induce fewer hemorrhagic side effects. Our aim is to assess the safety of intramuscular administration of influenza vaccine in patients on oral anticoagulation therapy. METHODS DESIGN Randomised, controlled, single blinded, multi-centre clinical trial. SETTING 4 primary care practices in Barcelona, Spain. PARTICIPANTS 229 patients on oral anticoagulation therapy eligible for influenza vaccine during the 2003-2004 season. INTERVENTIONS intramuscular administration of influenza vaccine in the experimental group (129 patients) compared to subcutaneous administration in the control group (100 patients). PRIMARY OUTCOME change in the circumference of the arm at the site of injection at 24 hours. SECONDARY OUTCOMES appearance of local reactions and pain at 24 hours and at 10 days; change in INR (International Normalized Ratio) at 24 hours and at 10 days. Analysis was by intention to treat using the 95% confidence intervals of the proportions or mean differences. RESULTS Baseline variables in the two groups were similar. No major side effects or major haemorrhage during the follow-up period were reported. No significant differences were observed in the primary outcome between the two groups. The appearance of local adverse reactions was more frequent in the subcutaneous administration group (37,4% vs. 17,4%, 95% confidence interval of the difference 8,2% to 31,8%). CONCLUSION This study shows that the intramuscular administration route of influenza vaccine in patients on anticoagulant therapy does not have more side effects than the subcutaneous administration route. REGISTRATION NUMBER NCT00137579 at clinicaltrials.gov.