Efficacy of Early Terlipressin Plus Albumin Therapy in Comparison to Standard Treatment for HRS-AKI in Acute-on-chronic Liver Failure.
Keywords
Abstract
Description
Aim To compare the effect of Early initiation of Terlipressin (ET arm) to albumin at 12 hour in ACLF patients with non-volume responsive AKI versus standard Terlipressin (ST arm) at 48 hours.
Primary Objective Efficacy of early terlipressin infusion in comparison to Standard treatment for resolution of AKI at day 7.
Secondary Objectives
- Full and partial AKI response at 48 and 72 h and 96 hours
- Mortality at Day 28, Day 90
- Baseline organ failure(s), MELD, CLIF-SOFA score and ACLF score
- New onset organ failures
- Urine Output
- Progression or resolution of OFs at day 7
- Change in MELD, CLIF-SOFA score and ACLF score at day 7
- Change in NGAL, FENa, FE-Urea at day 7
- Treatment related adverse effects and their grades
Methodology:
Study population:
All patients admitted to the Institute of Liver and Biliary Sciences (ILBS) with ACLF with AKI- HRS will be evaluated for inclusion. ACLF will be defined by the APASL criteria.
Study Design A prospective, randomized, single center open label study
Study Period:Two year
Intervention & monitoring:
Clinical Protocol An informed consent will be taken from ACLF patients with AKI within 24-hours of admission. No alteration in the treatment or investigative procedures of the included patients will be done. All included patients will be followed from admission till death or discharge. All discharged patients will then be followed till 30-days.
Preliminary work up
At admission:
(A) Complete history and physical examination
- Recent Diuretics use
- Loose stools
- Recurrent vomiting
- Fever, signs of sepsis (SIRS)
- H/s/o LRTI, SSTI, SBP
- Recent contrast use (< 7 days)
- Use of nephrotoxins including NSAIDs
- Prior renal dysfunction, known CKD, HD
- History of HTN, Diabetes
- History of renal stones
- History s/o hypotensive episodes (shock)
Pre-randomization interventions:
(B) Intervention during 0-12 hours (Before randomization) -
- Withdrawal of diuretics
- Withdrawal of lactulose (in patients with loose stools)
- Urine output monitoring (catheterize and monitor hourly or 12 h cumulative)
- 2 hourly MAP, Pulse rate
- Empirical IV antibiotics to be given in case of suspected/proven sepsis (Avoid nephrotoxic drugs e.g Amikacin, Colistin, Amphotericin etc as possible)
- IV hydration with albumin at 12 hours preferably 40 g (20 %) + 500 ml crystalloids)
Labs and follow-up:
- Baseline (at admission) - Blood : KFT, LFT, CBC, INR, Blood c/s, pro-BNP Imaging : USG abdomen, USG KUB, Renal doppler, C-X-ray, 2D ECHO Urine : Urine R/E and cultures, Urine Na, Urea, NGAL, Creatinine, FENa, FE Urea A/F analysis - for SBP
- At 12 hours (Before randomization) - Blood - KFT
- At D1, D2, D3, D5, D7, D14, D28 post randomization Blood : KFT Urine : Urine Na, Urea, NGAL, Creatinine, FENa, FE Urea (At Day 3 and 7) Imaging : Renal doppler (Day 3)
Clinical evaluation:
- Etiology of cirrhosis (Baseline)
- Severity of liver disease (Baseline, D3, D7) MELD score, CLIF-SOFA score, MELD-Na score, AARC score
- Stage of ACLF (Baseline,D3, D7) AARC grade, CLIF ACLF grade
- Complications / Organ failures (Baseline,D3, D7) HE, Bleed, AKI stage, SBP, Infection (specify site and severity) Respiratory and circulatory failure
Follow up duration Duration of admission till discharge or death will be noted. Patients will be followed up to 28-days for re-admission(s) and survival.
Dates
| Last Verified: | 05/31/2020 |
| First Submitted: | 05/31/2020 |
| Estimated Enrollment Submitted: | 05/31/2020 |
| First Posted: | 06/03/2020 |
| Last Update Submitted: | 05/31/2020 |
| Last Update Posted: | 06/03/2020 |
| Actual Study Start Date: | 06/09/2020 |
| Estimated Primary Completion Date: | 06/09/2022 |
| Estimated Study Completion Date: | 06/09/2022 |
Condition or disease
Intervention/treatment
Drug: Terlipressin + Albumin
Biological: Albumin
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Terlipressin + Albumin Injection terlipressin 2 mg/24 hours infusion + i/v albumin 1g/Kg/day | Drug: Terlipressin + Albumin Injection terlipressin 2 mg/24 hours infusion |
| Active Comparator: Albumin i/v albumin 1g/Kg/day for next 36 hours f/b inj terlipressin 2mg/24 hours |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: 1. Age 18-65 years 2. ACLF as per APASL criteria 3. AKI at admission as defined by ICA-AKI criteria 4. AKI stage 2/3 at 12 hour of admission Exclusion Criteria: - At Admission: - Age <18 years - Patients on renal replacement therapy (RRT) - Post renal or liver transplantation - History of CAD, ischemic cardiomyopathy, PVD, ventricular arrhythmia - Decompensated cirrhosis not fulfilling ACLF criteria - Cirrhotics with AKI managed as outpatients - Grade III/IV HE or Shock requiring inotropes or patients on mechanical ventilator at time of randomization - In-hospital new AKI - Active urinary sediments - 2+ albumin or above, dysmorphic RBCs - Known CKD, obstructive uropathy - Lack of informed consent - Prior intolerance or S/E to Terlipressin or albumin At 12 Hour before randomization: • Regression of AKI (>0.3 mg/dl) above baseline after IV albumin (20% 40 gm) + IV Crystalloids 500 ml therapy for 12 hours |
Outcome
Primary Outcome Measures
1. Acute Kidney Injury reversal by day 7 in both groups [Day 7]
Secondary Outcome Measures
1. Mortality in both groups [Day 28]
2. Mortality in both groups [Day 90]
3. Progression or resolution of Organ failures [Day 90]
4. Adverse Events in both groups [Day 90]
