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

This study is currently recruiting participants.
Verified September 2017 by Mallinckrodt
Sponsor:
ClinicalTrials.gov Identifier:
NCT02770716
First Posted: May 12, 2016
Last Update Posted: September 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Watermark
Information provided by (Responsible Party):
Mallinckrodt
May 10, 2016
May 12, 2016
September 25, 2017
July 13, 2016
November 2019   (Final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT02770716 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
A Study To Confirm Efficacy and Safety of Terlipressin in HRS Type 1
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)
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.
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.
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hepatorenal Syndrome
  • 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
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
300
November 2019
November 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adults with cirrhosis and ascites
  • Rapidly progressive worsening in renal function to a serum creatinine (SCr) ≥2.25 mg/dL and meeting a trajectory for SCr to double over 2 weeks
  • 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
  • Estimated life expectancy of less than 3 days.
  • TIPS within 30 days of randomization.
  • Use of vasopressors (eg, norepinephrine, epinephrine or vasopressin, dopamine or other vasopressors) of at least 3 consecutive days within prior 14-day screening period. Patients receiving a vasopressor other than midodrine within 24 hours of qualifying SCr are excluded, ie, a 24-h washout is required prior to enrollment. Note: Patients receiving midodrine and octreotide may be enrolled. Midodrine and octreotide treatment must be stopped prior to randomization.
  • Known allergy or sensitivity to terlipressin or another component of the study treatment.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Shane Cole 800-556-3314 clinicaltrials@mallinckrodt.com
Canada,   United States
 
 
NCT02770716
MNK19013058
Yes
Not Provided
Not Provided
Mallinckrodt
Mallinckrodt
Watermark
Study Director: Khurram Jamil, MD Mallinckrodt
Mallinckrodt
September 2017

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