Clinical Trial Results:
An Exploratory Study to Investigate the Haemodynamic Effects of Serelaxin (RLX030) in Patients With Compensated Cirrhosis and Portal Hypertension
Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
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Summary
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EudraCT number |
2012-000236-26 |
Trial protocol |
GB |
Global end of trial date |
19 Dec 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Mar 2016
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First version publication date |
28 Mar 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CRLX030X2201
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01640964 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, trialandresults.registries@novartis.com
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, trialandresults.registries@novartis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 Dec 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Dec 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
• Part A (Magnetic resonance angiography (MRA))
To investigate whether serelaxin increases the total renal arterial blood flow in patients
with cirrhosis and PHT after at least 120 min of infusion (60 min at 80 μg/kg/day and at
least 60 min at 30 μg/kg/day).
• Part B (direct venous pressure measurement)
To investigate whether serelaxin reduces the PPG in patients with cirrhosis, PHT and a
TIPSS in situ after at least 120 min of infusion (60 min at 80 μg/kg/day and at least 60
min at 30 μg/kg/day).
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
Rescue medication to treat severe or serious condition in the opinion of the investigator was allowed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Apr 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 46
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Worldwide total number of subjects |
46
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EEA total number of subjects |
46
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
38
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Out of 47 enrolled patients, 1 patient did not get randomized to Part A serelaxin arm ; patient withdrew consent due to failure of meeting an exclusion criterion for Part A prior to receiving the dose of study medication. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Part A: Terlipressin acetate | ||||||||||||||||||||||||
Arm description |
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Terlipressin acetate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
2 mg IV bolus injection
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Arm title
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Part A: Serelaxin (RLX030) | ||||||||||||||||||||||||
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 type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Serelaxin
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Investigational medicinal product code |
RLX030
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Other name |
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Pharmaceutical forms |
Concentrate for dispersion for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
IV infusion for 2-3 hours; duration of infusion depends on time required for completion of MRA data acquisition;
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Arm title
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Part B: Serelaxin (RLX030) | ||||||||||||||||||||||||
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 the Portal pressure gradient (PPG) data acquisition. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Serelaxin
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Investigational medicinal product code |
RLX030
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Other name |
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Pharmaceutical forms |
Concentrate for dispersion for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
IV infusion for approximately 2 hours
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Baseline characteristics reporting groups
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Reporting group title |
Part A: Terlipressin acetate
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Reporting group description |
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection. | ||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part A: Serelaxin (RLX030)
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Reporting group 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part B: Serelaxin (RLX030)
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Reporting group 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 the Portal pressure gradient (PPG) data acquisition. | ||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Part A: Terlipressin acetate
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Reporting group description |
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection. | ||
Reporting group title |
Part A: Serelaxin (RLX030)
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Reporting group 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 | ||
Reporting group title |
Part B: Serelaxin (RLX030)
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Reporting group 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 the Portal pressure gradient (PPG) data acquisition. | ||
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End point title |
Change from baseline of the blood flow for the total renal arteries (Study Part A (Serelaxin treatment group only)) [1] [2] | ||||||||
End point 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)
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End point type |
Primary
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End point timeframe |
Baseline, 120 min post serelaxin infusion
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical hypothesis testing for this endpoint. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was planned to be summarized only for reported treatment group (s) in the table. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from baseline of the portal pressure gradient (PPG) (Study Part B) [3] [4] | ||||||||
End point 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).
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End point type |
Primary
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End point timeframe |
Baseline, 120 min post-infusion start
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical hypothesis testing for this endpoint. [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was planned to be summarized only for reported treatment group (s) in the table. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from baseline of the blood flow for the total renal arteries (Study Part A (Terlipressin Acetate group only)) [5] | ||||||||
End point 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)
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End point type |
Secondary
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End point timeframe |
Baseline, 120 min post infusion
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| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was planned to be summarized only for reported treatment group (s) in the table. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from baseline of the blood flow for the hepatic artery (Study Part A (Serelaxin treatment group only)) [6] | ||||||||
End point 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).
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End point type |
Secondary
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End point timeframe |
Baseline, 120 min post-infusion
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| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was planned to be summarized only for reported treatment group (s) in the table. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from baseline of the blood flow for the superior mesenteric artery (Study Part A (Serelaxin treatment group only)) [7] | ||||||||
End point 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).
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End point type |
Secondary
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End point timeframe |
Baseline, 120 min post-infusion
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| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was planned to be summarized only for reported treatment group (s) in the table. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from baseline of the blood flow for the descending thoracic aorta (Study Part A (Serelaxin treatment group only)) [8] | ||||||||
End point 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).
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End point type |
Secondary
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End point timeframe |
Baseline, 120 min post-infusion
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| Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was planned to be summarized only for reported treatment group (s) in the table. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from baseline of the blood flow for the portal vein (Study Part A (Serelaxin treatment group only)) [9] | ||||||||
End point 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).
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End point type |
Secondary
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End point timeframe |
Baseline, 120 min post-infusion
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| Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was planned to be summarized only for reported treatment group (s) in the table. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from baseline of the portal vein pressure (PVP) (Study Part B) [10] | ||||||||
End point 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).
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End point type |
Secondary
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End point timeframe |
Baseline, 120 min post infusion
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| Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was planned to be summarized only for reported treatment group (s) in the table. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of patients with total adverse events, serious adverse and death as assessment of safety and tolerability of serelaxin [11] | ||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
4 weeks
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| Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was planned to be summarized only for reported treatment group (s) in the table. |
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Part A - Serelaxin (RLX030)
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Reporting group 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part B - Serelaxin (RLX030)
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Reporting group 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 the Portal pressure gradient (PPG) data acquisition. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part A - Terlipressin acetate
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Reporting group description |
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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10 Oct 2014 |
The reasons for this amendment were to correct the minimum number of patients required for Part A and to modify the number of patients that would be enrolled into Part B. For Part A, the changes to the minimum values did not affect the statistical rationale as these minimum numbers were well below the number currently enrolled in Part A. For Part B, 10 patients had originally been planned (above the minimum of six required), as they were expected to have been enrolled within a reasonable time frame. However, during the course of the trial, it became apparent that a significant number of patient candidates for Part B had advanced to a
disease stage where certain exclusion criteria were then limiting factors for recruitment, including low blood pressure (SBP <110 mmHg) and requirement for diuretics. Additionally, the PPG ‘window’ for treatment (between 5 and 12 mmHg in most patients) had proven to be rather narrow. Thus, for clinical enrollment reasons, the decision was made to reduce the number of patients enrolled in Part B from ten to six. The statistical rationale was not affected; six patients represented the minimum required for the 90% CI on mean change from Baseline to exclude zero for each endpoint (PPG gradient, PVP, RAP). |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
