Early versus standard initiation of terlipressin for HRS-AKI in ACLF patients- a randomized controlled trial (ETERLI).

Abstract

Background and Aim: Terlipressin infusion has been shown to be effective in treatment of HRS-AKI. Progression of AKI is rapid in ACLF patients. Response to terlipressin correlates with stage of AKI and ACLF. Aims: We investigated whether early initiation of therapy might improve response to terlipressin in HRS-AKI patients by day 7. Methods: Consecutive ACLF patients with stage II/III AKI despite albumin resuscitation(40g) for 12 hours were randomized to receive early terlipressin at 2mg/24 hour plus albumin (ET, n=35) or standard therapy (ST, n=35), albumin alone for 48h followed by terlipressin. The primary end-point was AKI reversal by day 7. The main secondary end-points included need for dialysis, treatment-related adverse effects and mortality at day 28 and Day 90. Results: Baseline parameters including AKI stage and ACLF AARC scores in two groups were comparable. Full AKI response at day 7 was observed in 24/35 (68.6%) patients in ET group compared to 14/35(40 %) in ST group [P-0.03]. There was significant improvement in ACLF grades from baseline to Day 7 in ET group (ACLF grade II to I in 16 patients). Five patients in each group developed progressive AKI requiring dialysis. Significantly more patients died in ST group (23/35; 65.7 %) within 28 days compared to 14/35 (40 %) in ET group [P-0.031]. The 90-day mortality in ST group was higher (69.6% vs. 57.2%; P-0.071). Baseline MELD score [HR: 0.987 (95% CI: 0.864-3.211); P-0.02], HE at presentation [HR: 4.405 (95% CI: 1.776-10.927); P-0.001] and admission BUN [HR: 1.007 (95% CI: 1.000-1.013); P-0.036] were independent predictors of 28-day mortality. Overall, 9 patients had terlipressin related adverse effects, none was life threatening. Conclusion: In patients with ACLF, early initiation of terlipressin for AKI persisting despite 12 hours of volume expansion with albumin helps in early reversal of AKI and regression of ACLF stage with significantly short-term mortality benefit.