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

This study is currently recruiting participants.

See

Contacts and Locations

Verified July 2017 by Mallinckrodt

Sponsor:

Collaborator:

Watermark

Information provided by (Responsible Party):

Mallinckrodt

ClinicalTrials.gov Identifier:

NCT02770716

First received: May 10, 2016

Last updated: July 14, 2017

Last verified: July 2017

History of Changes

Tracking Information

First Received Date ^ICMJE

May 10, 2016

Last Updated Date

July 14, 2017

Start Date ^ICMJE

May 2016

Estimated Primary Completion Date

January 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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.

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT02770716 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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 ]

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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)

Brief Summary

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.

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.

Study Type ^ICMJE

Interventional

Study Phase

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment

Condition ^ICMJE

Hepatorenal Syndrome

Intervention ^ICMJE

Drug: Terlipressin acetate
Lyophilized terlipressin acetate, 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

Study Arms

Experimental: Terlipressin
Lyophilized terlipressin acetate, IV, 1 mg by bolus injection q 6 hours

Intervention: Drug: Terlipressin acetate
Placebo Comparator: Placebo Comparator
Placebo, IV, 1 mg by bolus injection q 6 hours

Intervention: Other: Placebo Comparator

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

300

Estimated Completion Date

January 2020

Estimated Primary Completion Date

January 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Senior)

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Shane Cole

908-238-5649

shane.cole@mallinckrodt.com

Listed Location Countries ^ICMJE

Canada, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT02770716

Other Study ID Numbers ^ICMJE

MNK19013058

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement

Not Provided

Responsible Party

Mallinckrodt

Study Sponsor ^ICMJE

Mallinckrodt

Collaborators ^ICMJE

Watermark

Investigators ^ICMJE

Study Director:

Khurram Jamil, MD

Mallinckrodt

PRS Account

Mallinckrodt

Verification Date

July 2017

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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