title: The safety and efficacy of the tetanus vaccine intramuscularly versus subcutaneously in anticoagulated patients: a randomized clinical trial.
abstract: BACKGROUND
  In patients treated with oral anticoagulants, subcutaneous injections of anti-tetanus vaccine are usually recommended to reduce the risk of bleeding, although the effectiveness of the vaccine has only been proven for intramuscular injection. The objective of this study was to compare the safety and efficacy of intramuscular and subcutaneous injections of tetanus-diphtheria vaccine in patients treated with oral anticoagulants.
  
  
  METHODS
  We present a prospective, double blinded, clinical trial comparing two groups of patients with oral anticoagulants: one group was administered tetanus-diphtheria vaccine by intramuscular injection, while the other was administered the same vaccine by subcutaneous injection. Allocation to each group was randomized and the duration of the study was six years.
  
  
  METHODS
  all patients treated with oral anticoagulants, who had been administered with at least one dose of vaccine, at 15 Health Centres in Vigo (Spain), and who agreed to participate in the study. The sample size was 115 patients in each group. The main variables for the safety analysis were the measurement of the brachial diameter, the appearance of basic injuries at the vaccine administration site, the appearance of pain and systemic reactions. The variable used for the efficacy analysis was a significant increase in the titres of anti-tetanus toxoid antibodies.An Intention-to-treat analysis will be performed. Details will be classified according to the administration route, while within each group a 3-tiered stratification will be defined by the administered number of doses. As a measure of association, relative risk will be estimated; the reduction of relative risk will also measured. For safety and to control the confounder effect, a logistic regression analysis will be carried out. As a measure of impact the reduction of absolute risk in relation to the total number of patients to be treated and the Number Needed to Treat will be estimated.CONSORT 2010 guidelines were applied for reporting parallel group randomised trials.
  
  
  CONCLUSIONS
  The most significant difficulties on the project are related to the large number of participating centres, required to obtain a viable study population sample size, and the coordination given the scattering of the centres and researchers.
  
  
  BACKGROUND
  ISRCTN69942081.
authors.affiliation: Sárdoma Primary Care Health Centre, EOXI Vigo, Galician Health Service, Red Española de Investigación en Atención Primaria (Spanish Primary Care Research Network, REDIAPP), (Baixada a Laxe 76), Vigo (36204), Spain. Fernando.Isidro.Lago.Deibe@sergas.es.
authors.forename: Fernando I
authors.initials: FI
authors.lastname: Lago-Deibe
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Martín-Miguel
authors.forename: Carmen
authors.initials: C
authors.lastname: Velicia-Peñas
authors.forename: Isabel Rey
authors.initials: IR
authors.lastname: Gómez-Serranillos
authors.forename: Manuela
authors.initials: M
authors.lastname: Fontanillo-Fontanillo
mesh_terms: D000906:Antibodies / Q000276:immunology; D000925:Anticoagulants / Q000009:adverse effects; D004165:Diphtheria / Q000517:prevention & control; D022422:Diphtheria-Tetanus Vaccine / Q000008:administration & dosage*; D004311:Double-Blind Method; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007273:Injections, Intramuscular / Q000009:adverse effects; D007279:Injections, Subcutaneous; D019934:International Normalized Ratio; D011320:Primary Health Care; D013742:Tetanus / Q000276:immunology / Q000517:prevention & control*; D013745:Tetanus Toxoid / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D022422:Diphtheria-Tetanus Vaccine; D013745:Tetanus Toxoid