Analysis of the intermediate results of the INVENT-1 clinical trial: open-label, randomized, multicenter study

Abstract

Background. Attempts to treat tuberculosis (TB) with the help of intravenous drugs have been made since the early XX century. However, XXI century medicine recommends treating TB with pills, and invasive anti-TB drugs (ATBD) are rarely used. International expert groups recommend intravenous administration only for critically ill patients or for patients with absorption disorders. Meanwhile, the advantages of intravenous ATBD include direct monitoring of treatment, accurate dosing for each patient, fewer side effects, and avoidance of taking a large number of tablets. Objective. To evaluate the efficacy, safety, and tolerability of intravenous and oral administration of ATBD in the intensive phase of treatment in patients with advanced destructive pulmonary TB with bacterial excretion. Materials and methods. The study involved 318 patients from 9 clinical centres. The total duration of the study was 18 months. Intravenous and oral administration of isoniazid, rifampicin and ethambutol were compared. The intensive phase of the study lasted 2 months, the maintenance phase lasted 4 months. Inclusion criteria were the following: age 18-65 years, diagnosis of pulmonary TB, at least one positive test result for TB mycobacteria, radiological confirmation of lung destruction and advance TB process, in women – negative urine test for pregnancy, informed consent, negative GenXpert MTB/RIF analysis, and verbal consent to abstain from alcohol during the study. Results and discussion. Due to the resistance to 1st line drugs 14 people were excluded from the study, due to the lack of data on culture – 16 people, for other reasons – 7 people. In the infusion treatment group, 52.63 % had disseminated TB, and 47.37 % had infiltrative TB. In the group of tablet treatment disseminated TB occurred in 35.2 % of patients, infiltrative – in 61.8 %, miliary – in 3 %. At 4th visit, the efficacy of abacillation in both treatment groups was comparable: 34.2 % in the infusion group and 35.26 % in the oral treatment group. But as of the 6th visit, the share of abacillation in the infusion group was 57.42 %, and in the oral treatment group – 46.96 %. Analysis of the time needed to achieve a negative result on mycobacterium TB also revealed the benefits of infusions. Thus, up to the 3rd visit this parameter was reached by 15.78 % of the infusion group patients, and by 13.76 % of oral therapy group patients. The total proportion of patients with a negative test for mycobacterium TB and clinical improvement in the infusion group was 60 %, and in the oral therapy group – 52.90 %. In infiltrative TB, 27.8 % of the infusion group and only 9.5 % of the tablet therapy group reached abacillation by the 3rd visit. In disseminated TB, abacillation was achieved up to 3rd visit in 5 % of the infusion group and 8.3 % of the tablet treatment group, however, the total numbers at the end of the study were 45 and 25 %, respectively. Conclusions. 1. Monitoring the patient’s treatment is a cornerstone of TB therapy. 2. There is a tendency to the greater effectiveness of TB treatment using intravenous ATBD in the intensive phase of therapy. 3. It is necessary to analyze the long-term results of treatment and the impact of both treatment regimens on the recurrence of the process.