Early Qtc Interval and Pancreatic Enzyme Changes with Bedaquiline Therapy in Multidrug-Resistant Tuberculosis: A Prospective Cohort Study

Abstract

Background: Bedaquiline is now central to multidrug-resistant tuberculosis (MDR-TB) therapy, but its use is tempered by concerns over QTc interval prolongation and, more recently, pancreatic enzyme elevation. Prospective data linking both signals within the same patients at a defined early time point remain limited, particularly from Indian programmatic settings.

Objectives: To assess changes in QTc interval and serum pancreatic enzymes (amylase, lipase) before and after one month of bedaquiline-containing therapy, to determine their correlation, and to identify associated demographic or clinical factors.

Methods: This prospective observational cohort study was conducted at the Chest and TB Hospital, Government Medical College, Amritsar, over 18 months. Seventy-three MDR-TB patients initiated on bedaquiline-containing regimens underwent 12-lead ECG and serum amylase/lipase estimation at baseline and after one month. Paired t-test compared baseline and follow-up values; Spearman correlation assessed the QTc–enzyme relationship; chi-square test examined associations with demographic and clinical variables.

Results: Mean QTc increased from 413.95±16.70 ms to 437.64±27.70 ms (mean difference 23.70 ms; 95% CI 18.89–28.51; p<0.001); 42.5% of patients developed QTc prolongation ≥30 ms, and 5.5% exceeded 500 ms, with no life-threatening arrhythmia. Serum amylase (83.51±11.50 to 97.34±20.51 U/L) and lipase (46.1±12.4 to 54.3±15.2 U/L) both rose significantly (p<0.001); 53.4% of patients showed mild (1–2× upper limit of normal) enzyme elevation, all asymptomatic. Change in QTc did not correlate with change in amylase (ρ=−0.18, p=0.13) or lipase (ρ=0.12, p=0.33). No demographic or clinical variable was significantly associated with QTc prolongation. Nausea/vomiting (24.7%) was the commonest additional adverse effect; 49.3% of patients reported none.

Conclusions: Bedaquiline is associated with significant early, largely subclinical, cardiac and pancreatic biochemical changes that occur independently of one another and of baseline risk profile. These findings support universal ECG monitoring and targeted biochemical surveillance for all patients initiating bedaquiline.