Back to resultsAn Exploratory Haemodynamic Study in Patients With Compensated Cirrhosis and Portal Hypertension
Primary Purpose
Compensated Cirrhosis and Portal Hypertension
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Terlipressin acetate
Serelaxin (RLX030)
Sponsored by
About this trial
This is an interventional treatment trial for Compensated Cirrhosis and Portal Hypertension focused on measuring Portal hypertension, cirrhosis, TIPSS, MRI, MRA, portal pressure, portal pressure gradient
Eligibility Criteria
Inclusion Criteria:
Study Parts A and B:
-Cirrhosis of alcohol aetiology according to physician's assessment prior to screening.
Part A:
-Cirrhosis with clinical and/or endoscopic evidence of portal hypertension (e.g. oesophageal varices).
Part B:
- Cirrhosis with TIPSS in situ and PPG>5mmHg.
- Fully functioning TIPSS without variceal filling as confirmed by portography.
Exclusion Criteria:
Study Parts A and B:
- Use of any drug to treat portal hypertension (e.g. vasodilators such as non-selective beta blockers or nitrates) within 1 month prior to screening.
- Decompensated cirrhosis (Child-Pugh score >9 points, and/or ascites requiring diuretics, and/or hepatic encephalopathy) at visit 1.
- Presence of any non-controlled and clinically significant disease that could affect the study outcome or that would place the patient at undue risk.
Part A:
- BMI (weight[kg] / height[m^2]) > 40 kg/m^2.
- Any contraindication to having an MRI scan
Part B:
-Contraindication to catheterization
Sites / Locations
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part A: Terlipressin acetate
Part A: Serelaxin (RLX030)
Part B Serelaxin (RLX030)
Arm Description
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection.
Randomized patients received an intravenous serelaxin infusion at two different infusion rates: 80 μg/kg/day for 60 min followed by 30 μg/kg/day for at least 60 min.; duration of infusion depends on time required for completion of magnetic resonance angiography (MRA) data acquisition
The patients enrolled in this part of the study received an intravenous (iv) serelaxin infusion at two different infusion rates: 80 μg/kg/day for 60 min followed by 30 μg/kg/day for at least 60 min; duration of infusion depends on time required for completion of Portal pressure gradient (PPG) data acquisition.
Outcomes
Primary Outcome Measures
Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Serelaxin Treatment Group Only))
The flow is the average flow over the cardiac cycle. Total renal artery flow = left renal artery flow + right renal artery flow. These measurements were collected through magnetic resonance angiography (MRA) scans. Baseline blood flow for total renal artery is measured at pre-dose (Day 1, 0 min post-treatment)
Change From Baseline of the Portal Pressure Gradient (PPG) (Study Part B)
Direct venous pressure was measured by portal pressure gradient (PPG). PPG = portal vein pressure (PVP) - inferior vena cava pressure (IVCP).
Baseline blood flow for PPG was measured at pre-dose (Day 1, 0 min post-treatment). PVP was measured at 15 min intervals (i.e. prior to and at 15, 30, 45, 60, 75, 90, 105, and 120 min of serelaxin infusion).
Secondary Outcome Measures
Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Terlipressin Acetate Group Only))
The flow is the average flow over the cardiac cycle. Total renal artery flow = left renal artery flow + right renal artery flow. These measurements were collected through magnetic resonance angiography (MRA) scans. Baseline blood flow for total renal artery is measured at pre-dose (Day 1, 0 min post-treatment)
Change From Baseline of the Blood Flow for the Hepatic Artery (Study Part A (Serelaxin Treatment Group Only))
A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as hepatic artery. The flow is the average flow over the cardiac cycle.
Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment).
Change From Baseline of the Blood Flow for the Superior Mesenteric Artery (Study Part A (Serelaxin Treatment Group Only))
A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as superior mesenteric artery. The flow is the average flow over the cardiac cycle.
Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment).
Change From Baseline of the Blood Flow for the Descending Thoracic Aorta (Study Part A (Serelaxin Treatment Group Only))
A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as descending thoracic aorta. The flow is the average flow over the cardiac cycle.
Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment).
Change From Baseline of the Blood Flow for the Portal Vein (Study Part A (Serelaxin Treatment Group Only))
A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as the portal vein. The flow is the average flow over the cardiac cycle.
Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment).
Change From Baseline of the Portal Vein Pressure (PVP) (Study Part B)
Portal vein pressure was measured at 15 min intervals (i.e. prior to and at 15, 30, 45, 60, 75, 90, 105, and 120 min of serelaxin infusion).
Number of Patients With Total Adverse Events, Serious Adverse and Death as Assessment of Safety and Tolerability of Serelaxin
This endpoint reports patients with any adverse event, serious adverse event and death for the serelaxin group of Part A and Part B of the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01640964
Brief Title
An Exploratory Haemodynamic Study in Patients With Compensated Cirrhosis and Portal Hypertension
Official Title
An Exploratory Study to Investigate the Haemodynamic Effects of Serelaxin (RLX030) in Patients With Compensated Cirrhosis and Portal Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main purpose of this exploratory study was to investigate the effect of serelaxin (RLX030) infusion on the hepatic and renal circulation in patients with compensated cirrhosis and portal hypertension. Measurements were acquired non-invasively using magnetic resonance angiography (MRA) (study part A) and more directly via cannulation of the hepatic portal vein during a routine transjugular intrahepatic portosystemic shunt (TIPSS) check procedure (study part B), to determine the acute haemodynamic response to serelaxin (RLX030).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Compensated Cirrhosis and Portal Hypertension
Keywords
Portal hypertension, cirrhosis, TIPSS, MRI, MRA, portal pressure, portal pressure gradient
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A: Terlipressin acetate
Arm Type
Experimental
Arm Description
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection.
Arm Title
Part A: Serelaxin (RLX030)
Arm Type
Experimental
Arm Description
Randomized patients received an intravenous serelaxin infusion at two different infusion rates: 80 μg/kg/day for 60 min followed by 30 μg/kg/day for at least 60 min.; duration of infusion depends on time required for completion of magnetic resonance angiography (MRA) data acquisition
Arm Title
Part B Serelaxin (RLX030)
Arm Type
Experimental
Arm Description
The patients enrolled in this part of the study received an intravenous (iv) serelaxin infusion at two different infusion rates: 80 μg/kg/day for 60 min followed by 30 μg/kg/day for at least 60 min; duration of infusion depends on time required for completion of Portal pressure gradient (PPG) data acquisition.
Intervention Type
Drug
Intervention Name(s)
Terlipressin acetate
Intervention Description
IV bolus injection
Intervention Type
Drug
Intervention Name(s)
Serelaxin (RLX030)
Intervention Description
Part A2: IV infusion for 2-3 hours; duration of infusion depends on time required for completion of MRA data acquisition; Part B: IV infusion for approximately 2 hours
Primary Outcome Measure Information:
Title
Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Serelaxin Treatment Group Only))
Description
The flow is the average flow over the cardiac cycle. Total renal artery flow = left renal artery flow + right renal artery flow. These measurements were collected through magnetic resonance angiography (MRA) scans. Baseline blood flow for total renal artery is measured at pre-dose (Day 1, 0 min post-treatment)
Time Frame
Baseline, 120 min post serelaxin infusion
Title
Change From Baseline of the Portal Pressure Gradient (PPG) (Study Part B)
Description
Direct venous pressure was measured by portal pressure gradient (PPG). PPG = portal vein pressure (PVP) - inferior vena cava pressure (IVCP).
Baseline blood flow for PPG was measured at pre-dose (Day 1, 0 min post-treatment). PVP was measured at 15 min intervals (i.e. prior to and at 15, 30, 45, 60, 75, 90, 105, and 120 min of serelaxin infusion).
Time Frame
Baseline, 120 min post-infusion start
Secondary Outcome Measure Information:
Title
Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Terlipressin Acetate Group Only))
Description
The flow is the average flow over the cardiac cycle. Total renal artery flow = left renal artery flow + right renal artery flow. These measurements were collected through magnetic resonance angiography (MRA) scans. Baseline blood flow for total renal artery is measured at pre-dose (Day 1, 0 min post-treatment)
Time Frame
Baseline, 120 min post infusion
Title
Change From Baseline of the Blood Flow for the Hepatic Artery (Study Part A (Serelaxin Treatment Group Only))
Description
A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as hepatic artery. The flow is the average flow over the cardiac cycle.
Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment).
Time Frame
Baseline, 120 min post-infusion
Title
Change From Baseline of the Blood Flow for the Superior Mesenteric Artery (Study Part A (Serelaxin Treatment Group Only))
Description
A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as superior mesenteric artery. The flow is the average flow over the cardiac cycle.
Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment).
Time Frame
Baseline, 120 min post-infusion
Title
Change From Baseline of the Blood Flow for the Descending Thoracic Aorta (Study Part A (Serelaxin Treatment Group Only))
Description
A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as descending thoracic aorta. The flow is the average flow over the cardiac cycle.
Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment).
Time Frame
Baseline, 120 min post-infusion
Title
Change From Baseline of the Blood Flow for the Portal Vein (Study Part A (Serelaxin Treatment Group Only))
Description
A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as the portal vein. The flow is the average flow over the cardiac cycle.
Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment).
Time Frame
Baseline, 120 min post-infusion
Title
Change From Baseline of the Portal Vein Pressure (PVP) (Study Part B)
Description
Portal vein pressure was measured at 15 min intervals (i.e. prior to and at 15, 30, 45, 60, 75, 90, 105, and 120 min of serelaxin infusion).
Time Frame
Baseline, 120 min post infusion
Title
Number of Patients With Total Adverse Events, Serious Adverse and Death as Assessment of Safety and Tolerability of Serelaxin
Description
This endpoint reports patients with any adverse event, serious adverse event and death for the serelaxin group of Part A and Part B of the study.
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Study Parts A and B:
-Cirrhosis of alcohol aetiology according to physician's assessment prior to screening.
Part A:
-Cirrhosis with clinical and/or endoscopic evidence of portal hypertension (e.g. oesophageal varices).
Part B:
Cirrhosis with TIPSS in situ and PPG>5mmHg.
Fully functioning TIPSS without variceal filling as confirmed by portography.
Exclusion Criteria:
Study Parts A and B:
Use of any drug to treat portal hypertension (e.g. vasodilators such as non-selective beta blockers or nitrates) within 1 month prior to screening.
Decompensated cirrhosis (Child-Pugh score >9 points, and/or ascites requiring diuretics, and/or hepatic encephalopathy) at visit 1.
Presence of any non-controlled and clinically significant disease that could affect the study outcome or that would place the patient at undue risk.
Part A:
BMI (weight[kg] / height[m^2]) > 40 kg/m^2.
Any contraindication to having an MRI scan
Part B:
-Contraindication to catheterization
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Edinburgh
ZIP/Postal Code
EH16 4TJ
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
28245243
Citation
Snowdon VK, Lachlan NJ, Hoy AM, Hadoke PW, Semple SI, Patel D, Mungall W, Kendall TJ, Thomson A, Lennen RJ, Jansen MA, Moran CM, Pellicoro A, Ramachandran P, Shaw I, Aucott RL, Severin T, Saini R, Pak J, Yates D, Dongre N, Duffield JS, Webb DJ, Iredale JP, Hayes PC, Fallowfield JA. Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial. PLoS Med. 2017 Feb 28;14(2):e1002248. doi: 10.1371/journal.pmed.1002248. eCollection 2017 Feb.
Results Reference
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An Exploratory Haemodynamic Study in Patients With Compensated Cirrhosis and Portal Hypertension
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