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A Study To Confirm Efficacy and Safety of Terlipressin in HRS Type 1

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Mallinckrodt
Sponsor:
Collaborator:
Watermark
Information provided by (Responsible Party):
Mallinckrodt
ClinicalTrials.gov Identifier:
NCT02770716
First received: May 10, 2016
Last updated: August 14, 2017
Last verified: August 2017
  Purpose
This study is to confirm the efficacy and safety of intravenous terlipressin versus placebo in the treatment of adult subjects with hepatorenal syndrome (HRS) Type 1.

Condition Intervention Phase
Hepatorenal Syndrome Drug: Terlipressin acetate Other: Placebo Comparator Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-Center, Randomized, Placebo Controlled, Double-Blind Study to Confirm Efficacy and Safety of Terlipressin in Subjects With Hepatorenal Syndrome Type 1 (The CONFIRM Study)

Resource links provided by NLM:


Further study details as provided by Mallinckrodt:

Primary Outcome Measures:
  • Verified HRS Reversal [ Time Frame: Up to 14 Days ]
    Defined as the percentage of subjects with 2 consecutive SCr values ≤1.5 mg/dL at least 2 hours apart.


Secondary Outcome Measures:
  • Incidence of subjects with HRS reversal [ Time Frame: Up to 14 Days ]
    Incidence of subjects with HRS reversal, defined as the percentage of subjects with a SCr value ≤1.5 mg/dL by Day 14 or discharge.

  • Durability of HRS reversal [ Time Frame: Day 30 ]
    Percentage of subjects with HRS reversal without RRT to Day 30.

  • Incidence of HRS Reversal in the systemic inflammatory response syndrome (SIRS) [ Time Frame: Day 14 ]

Estimated Enrollment: 300
Study Start Date: May 2016
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Terlipressin
Lyophilized terlipressin acetate, IV, 1 mg by bolus injection q 6 hours
Drug: Terlipressin acetate
Lyophilized terlipressin acetate, IV, 1 mg by bolus injection q 6 hours
Placebo Comparator: Placebo Comparator
Placebo, IV, 1 mg by bolus injection q 6 hours
Other: Placebo Comparator
11 mg mannitol reconstituted with 5 ml of sterile 0.9% sodium chloride solution

Detailed Description:
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter pivotal trial of terlipressin in subjects with HRS type 1. HRS is a rare syndrome of marked renal dysfunction in patients with cirrhosis, decompensated liver disease, and portal hypertension. HRS type 1 is characterized by a rapid progressive renal impairment and has a very poor prognosis with >80% mortality within 3 months. At present, there are no approved drug therapies for HRS type 1 in the US or Canada. The only curative treatment for HRS type 1 and the underlying end-stage cirrhosis is liver transplantation. However, many patients will not survive long enough to receive a liver transplant. Increased understanding of the pathophysiology of HRS type 1 has demonstrated that vasoconstrictive drug therapy may reverse HRS type 1. Substantial data available from many published clinical investigations in the literature provide compelling evidence suggesting that administration of terlipressin improves renal function in patients with HRS. A total of 300 subjects are planned to be enrolled at approximately 70 sites in the US and Canada. An interim analysis is scheduled after 150 subjects are enrolled. The study will be stopped if the pre-specified threshold for efficacy criteria is met at interim analysis.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults with cirrhosis and ascites
  • Rapidly progressive worsening in renal function to a serum creatinine (SCr) ≥2.25 mg/dL
  • No sustained improvement in renal function (<20% decrease in SCr and SCr ≥2.25 mg/dL) at least 48 hours after diuretic withdrawal and the beginning of plasma volume expansion with albumin

Exclusion Criteria:

  • Serum creatinine level >7.0 mg/dL
  • At least 1 event of large volume paracentesis (LVP) ≥4 L within 2 days of randomization
  • Sepsis and/or uncontrolled bacterial infection
  • <2 days anti-infective therapy for documented or suspected infection
  • Shock
  • Current or recent (within 4 weeks) treatment with or exposure to nephrotoxic agents
  • Superimposed acute liver injury due to drugs (e.g., acetaminophen), dietary supplements, herbal preparations, viral hepatitis, or toxins
  • Proteinuria >500 mg/day
  • Evidence of obstructive uropathy or parenchymal renal disease on ultrasound or other imaging
  • Tubular epithelial casts, heme granular casts, hematuria or microhematuria
  • Confirmed pregnancy
  • Severe cardiovascular disease, including, but not limited to, unstable angina, pulmonary edema, congestive heart failure
  • Current or recent (within 4 weeks) renal replacement therapy (RRT)
  • Participation in other clinical research involving investigational medicinal products within 30 days of randomization
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02770716

Contacts
Contact: Shane Cole 800-556-3314 clinicaltrials@mallinckrodt.com

  Show 55 Study Locations
Sponsors and Collaborators
Mallinckrodt
Watermark
Investigators
Study Director: Khurram Jamil, MD Mallinckrodt
  More Information

Responsible Party: Mallinckrodt
ClinicalTrials.gov Identifier: NCT02770716     History of Changes
Other Study ID Numbers: MNK19013058
Study First Received: May 10, 2016
Last Updated: August 14, 2017

Additional relevant MeSH terms:
Terlipressin
Syndrome
Hepatorenal Syndrome
Disease
Pathologic Processes
Liver Diseases
Digestive System Diseases
Kidney Diseases
Urologic Diseases
Lypressin
Antihypertensive Agents
Vasoconstrictor Agents
Hemostatics
Coagulants
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 21, 2017