Open Access Study protocol

The safety and efficacy of the tetanus vaccine intramuscularly versus subcutaneously in anticoagulated patients: a randomized clinical trial

Fernando I Lago-Deibe1*, Maria-Victoria Martín-Miguel2, Carmen Velicia-Peñas1, Isabel Rey Gómez-Serranillos3 and Manuela Fontanillo-Fontanillo4

Author Affiliations

1 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

2 Matamá Primary Care Health Centre, Vigo Primary Care Region, EOXI Vigo, Galician Health Service, (Babio s/n), Vigo (36312), Spain

3 Quality Unit, EOXI Vigo, Galician Health Service, (Rosalía de Castro 21-23), Vigo (36201), Spain

4 Department of Statistics, Research Support Unit, EOXI Vigo, Spain

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BMC Family Practice 2014, 15:147  doi:10.1186/1471-2296-15-147

Published: 28 August 2014

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/design

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.

Study population: 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.

Discussion

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.

Trial registration

ISRCTN69942081.

Keywords:
Anticoagulants; Tetanus toxoid; Safety; Vaccines; Primary Health Care (Mesh Terms)