Terlipressin for HRS-AKI in Liver Transplant Candidates (INFUSE)

NCT04460560 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 834744
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 7

Brief Summary

Hepatorenal syndrome-acute kidney injury (HRS-AKI), a potentially reversible renal failure, is a serious, rapidly progressing, often fatal, complication of decompensated cirrhosis. Terlipressin is a synthetic vasopressin analogue that acts as a systemic vasoconstrictor via the vascular vasopressin V1 receptors. In HRS-AKI patients the strong V1 receptor-mediated vasoconstrictor activity of terlipressin, particularly in the splanchnic area, increases effective intravascular volume and mean arterial pressure (MAP), ameliorates renin-angiotensin-aldosterone system and sympathetic nervous system hyperactivity, and improves renal blood flow. The INFUSE trial will evaluate the use of continuous terlipressin infusion in patients on the liver transplant waiting list with HRS-AKI.

Conditions

Hepatorenal Syndrome

Outcome Measures

Primary Outcomes (1)

• Improvement of Renal Function (SCr) From Day 1 Thru End of Treatment, Repeated Measure Analysis. SCr Will be Collected Daily, From Day 1 Thru End of Treatment. Baseline SCr Will Also be Entered.

  SCr will be collected daily, from Day 1 thru end of treatment. Complete response (CR) defined as ≥30% decrease in SCr with EOT SCr≤1.5, partial response (PR) as ≥30% decrease in SCr with EOT SCr\>1.5, and non-response (NR) as \<30% decrease in SCr.

  14 days or reversal of HRS-AKI, whichever occur first

Study Arms (1)

Open-Label Terlipressin

OTHER

All prospective patients receive open-label Terlipressin.

Drug: Terlipressin

Interventions

Terlipressin DRUG

For the first dose of terlipressin, each vial will be reconstituted with 5 mL of sterile 0.9% sodium chloride solution and administered intravenously as a bolus injection and given over 1 minute at a dose of 0.5 mg. For continuous infusion, the dose of terlipressin is to be dissolved in 0.9% sodium chloride solution and infused with a pump

Open-Label Terlipressin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent by subject or legally authorized representative.
• At least 18 years of age.
• Cirrhosis and ascites.
• No sustained improvement in renal function (less than 20% decrease in SCr) at least 48 hours after diuretic withdrawal and after plasma volume expansion with albumin (given daily for two days - 48 hours minimum from 1st dose). If SCr improves by ≥ 20 % but plateaus ( ≤ 10 % fluctuation in sCr) and remains above 1.5 mg/dl for ≥another 48 hrs and there are no features of acute tubular necrosis.
• Increase in SCr by at least ≥ 0.3 mg/dl OR 1.5-2 fold above baseline (AKI stage 1 and above), to a SCr of ≥ 1.5 mg/dl at the time of initiating treatment. Baseline SCr is defined as the most recent, lowest SCr within last 6 months before date of current admission.
• A.On liver transplant wait list or liver transplant eligible with anticipation of being placed on the liver transplant wait list. B. Patients not on the transplant waitlist or transplant eligible are also eligible for the trial ( maximum 25 subjects) -

You may not qualify if:

• Serum creatinine level greater than 5.0 mg/dL. Subjects with value greater than 5.0 mg/dL may be enrolled with Sponsor prior approval.
• MELD score ≥ 35
• Acute on Chronic Liver Failure (ACLF) grade 3 (according to the CLIF Consortium grading system).
• Uncontrolled sepsis and/or uncontrolled bacterial infection (e.g., persisting bacteremia, persisting ascitic fluid leukocytosis, fever, increasing leukocytosis with vasomotor instability).
• Shock.
• Current or recent (within 4 weeks) treatment with or exposure to nephrotoxic agents: eg, aminoglycosides, amphotericin, cyclosporine A, cisplatin, nonsteroidal anti-inflammatory drugs (NSAIDs: e.g., ibuprofen, naproxen, diclofenac), significant exposure to radiographic contrast agents (large doses or multiple injections of iodinated contrast media; e.g., during coronary or abdominal angiogram).
• Estimated life expectancy of less than 7 days.
• Advanced Hepatocellular Carcinoma ( HCC) with expected survival of \< 6 months
• Superimposed acute liver injury due to drugs (e.g., acetaminophen), dietary supplements, herbal preparations, viral hepatitis, or toxins (e.g., Amanita toxin with mushroom poisoning carbon tetrachloride), with the exception of acute alcoholic hepatitis.
• Evidence of obstructive uropathy or parenchymal renal disease. Renal ultrasound or other imaging not required but should be taken if suspicious.
• Tubular epithelial casts, heme granular casts (range of 1-3 granular casts acceptable), hematuria or microhematuria on urinalysis that is indicative of acute tubular necrosis and/or intrinsic renal disease.
• Subjects known to be pregnant; all women of child-bearing age and potential must have a negative pregnancy test.
• Severe cardiovascular disease, including, but not limited to, unstable angina, pulmonary edema, congestive heart failure, or persisting symptomatic peripheral vascular disease, myocardial infarction or stable chronic angina within the past 12 months, or any other cardiovascular disease judged by the investigator to be severe and creates a risk to subject with concurrent terlipressin use.
• Current or recent (within 4 weeks) renal replacement therapy (RRT) or anticipation of RRT within 3 days on enrollment.
• Participation in other clinical research involving investigational medicinal products within 30 days of starting study drug that would adversely affect participation in this or the current trial.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (7)

California Pacific Medical Center

San Francisco, California, 94114, United States

Location

Piedmont Healthcare, Inc

Atlanta, Georgia, 30309, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor Scott and White All Saints Medical Center

Fort Worth, Texas, 76104, United States

Location

MeSH Terms

Conditions

Hepatorenal Syndrome

Interventions

Terlipressin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Lypressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: K. Rajender Reddy, MD
• Organization: University of Pennsylvania

ReddyR@pennmedicine.upenn.edu

215-662-4311

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 7, 2020
• Study Start: December 11, 2020
• Primary Completion: December 27, 2023
• Study Completion: December 27, 2023
• Last Updated: October 9, 2024
• Results First Posted: October 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)