Introduction of BCG vaccine as immunotherapy on pulmonary disease due to Mycobacterium avium complex: effectiveness determination (II phase): multicentre, superiority, randomized, double-blinded and controlled clinical trial

Abstract

Background Nontuberculous mycobacterium (NTM) infections are increasingly frequent due to the human engineering environment, the susceptibility of the hosts, and the improvement of diagnostic techniques to detect and typify them. The most common pathogenic specie is the Mycobacterium Avium complex, which usually causes chronic lung disease in immunocompetent patients. The current antimicrobial treatment is long (12-18 months), with high toxicity (due to the use of antituberculosis drugs), low cure taxa (50-55%) and high reinfection taxa (up to 40%). Recent studies have demonstrated the existence of cross-immunity between TBC and MAC from the application of BCG vaccines in multiple murine models, nonhuman primates and

human subjects. These studies have revealed an inhibition in the replication and growth of MAC- infected cells, opening a gap to induce the treatment of these patients with BCG immunotherapy.

Objective The purpose of the present study is to demonstrate the effectiveness of BCG vaccine against tuberculosis as induction immunotherapy for the treatment of pulmonary infections due to Mycobacterium Avium Complex. Methods Design and setting: A multicentre, superiority, randomized, double-blinded and controlled clinical trial will be performed among eight hospitals of Catalonia. Intervention: A stratified by radiological pattern sample will be performed in order to generate two therapy groups (A and B) with participants >18 years old. Patients from group A (n = 108) will receive intradermal placebo (two dose) followed by oral antibiotic until microbiological healing and 12 months since that moment while group B patients will be stratified in two groups that will receive two different dose of BCG vaccine followed by the same antibiotic guideline, group B-I (n = 108) and group B-II (n = 108). Treatment will last maximum 18 months, depending on the time it takes for the patient to reach microbiological healing (rarely happens after 6 months). Main outcome will be disease resolution, defined as the negativization of sputum culture and maintained disappearance of symptoms for at least twelve months since it occurs. One follow-up visit per month (4 weeks) will be scheduled after diagnosis for both groups, and will consist mainly in clinical examination of symptoms and monitoring of hepatic function, EKG and sputum culture