Trial Outcomes & Findings for An Exploratory Haemodynamic Study in Patients With Compensated Cirrhosis and Portal Hypertension (NCT NCT01640964)
NCT ID: NCT01640964
Last Updated: 2016-03-15
Results Overview
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)
COMPLETED
PHASE2
47 participants
Baseline, 120 min post serelaxin infusion
2016-03-15
Participant Flow
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.
Participant milestones
| Measure |
Part A: Terlipressin Acetate
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection.
|
Part A: Serelaxin (RLX030)
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
|
Part B: Serelaxin (RLX030)
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
20
|
20
|
6
|
|
Overall Study
COMPLETED
|
19
|
19
|
3
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
3
|
Reasons for withdrawal
| Measure |
Part A: Terlipressin Acetate
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection.
|
Part A: Serelaxin (RLX030)
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
|
Part B: Serelaxin (RLX030)
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.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
|
Overall Study
Protocol Deviation
|
1
|
1
|
2
|
Baseline Characteristics
An Exploratory Haemodynamic Study in Patients With Compensated Cirrhosis and Portal Hypertension
Baseline characteristics by cohort
| Measure |
Part A: Terlipressin Acetate
n=20 Participants
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection.
|
Part A: Serelaxin (RLX030)
n=20 Participants
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
|
Part B: Serelaxin (RLX030)
n=6 Participants
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.
|
Total
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
< 65 years
|
17 Patients
n=39 Participants
|
15 Patients
n=41 Participants
|
6 Patients
n=35 Participants
|
38 Patients
n=31 Participants
|
|
Age, Customized
>= 65 years
|
3 Patients
n=39 Participants
|
5 Patients
n=41 Participants
|
0 Patients
n=35 Participants
|
8 Patients
n=31 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=39 Participants
|
4 Participants
n=41 Participants
|
3 Participants
n=35 Participants
|
11 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=39 Participants
|
16 Participants
n=41 Participants
|
3 Participants
n=35 Participants
|
35 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Baseline, 120 min post serelaxin infusionPopulation: Full analysis set (FAS) included all patients who received any amount of study treatment during the treatment period and had at least one post-Baseline assessment during that period.
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)
Outcome measures
| Measure |
Part A: Serelaxin (RLX030)
n=20 Participants
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
|
Part B: Serelaxin (RLX030)
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.
|
|---|---|---|
|
Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Serelaxin Treatment Group Only))
|
0.438 L/min
Interval 0.274 to 0.601
|
—
|
PRIMARY outcome
Timeframe: Baseline, 120 min post-infusion startPopulation: For Part B of the study, full analysis set included all patients who received any amount of study treatment during the treatment period and had at least one post-baseline assessment during that period.Only patients with a value at both baseline and this time point are included.
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).
Outcome measures
| Measure |
Part A: Serelaxin (RLX030)
n=6 Participants
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
|
Part B: Serelaxin (RLX030)
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.
|
|---|---|---|
|
Change From Baseline of the Portal Pressure Gradient (PPG) (Study Part B)
|
-1.2 mmHg
Interval -6.1 to 3.7
|
—
|
SECONDARY outcome
Timeframe: Baseline, 120 min post infusionPopulation: Full analysis set (FAS) included all patients who received any amount of study treatment during the treatment period and had at least one post-Baseline assessment during that period.
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)
Outcome measures
| Measure |
Part A: Serelaxin (RLX030)
n=19 Participants
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
|
Part B: Serelaxin (RLX030)
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.
|
|---|---|---|
|
Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Terlipressin Acetate Group Only))
|
0.059 L/min
Interval -0.045 to 0.164
|
—
|
SECONDARY outcome
Timeframe: Baseline, 120 min post-infusionPopulation: For the part A of the study, full analysis set included all patients who received any amount of study treatment during the treatment period and had at least one post-baseline assessment during that period. Only patients with a value at both baseline and at the time point are included
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).
Outcome measures
| Measure |
Part A: Serelaxin (RLX030)
n=20 Participants
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
|
Part B: Serelaxin (RLX030)
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.
|
|---|---|---|
|
Change From Baseline of the Blood Flow for the Hepatic Artery (Study Part A (Serelaxin Treatment Group Only))
|
0.084 L/min
Interval -0.02 to 0.187
|
—
|
SECONDARY outcome
Timeframe: Baseline, 120 min post-infusionPopulation: For the part A of the study, full analysis set included all patients who received any amount of study treatment during the treatment period and had at least one post-baseline assessment during that period. Only patients with a value at both baseline and at the time point are included
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).
Outcome measures
| Measure |
Part A: Serelaxin (RLX030)
n=20 Participants
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
|
Part B: Serelaxin (RLX030)
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.
|
|---|---|---|
|
Change From Baseline of the Blood Flow for the Superior Mesenteric Artery (Study Part A (Serelaxin Treatment Group Only))
|
0.002 L/min
Interval -0.087 to 0.09
|
—
|
SECONDARY outcome
Timeframe: Baseline, 120 min post-infusionPopulation: For the part A of the study, full analysis set included all patients who received any amount of study treatment during the treatment period and had at least one post-baseline assessment during that period. Only patients with a value at both baseline and at the time point are included
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).
Outcome measures
| Measure |
Part A: Serelaxin (RLX030)
n=20 Participants
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
|
Part B: Serelaxin (RLX030)
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.
|
|---|---|---|
|
Change From Baseline of the Blood Flow for the Descending Thoracic Aorta (Study Part A (Serelaxin Treatment Group Only))
|
0.293 L/min
Interval 0.059 to 0.527
|
—
|
SECONDARY outcome
Timeframe: Baseline, 120 min post-infusionPopulation: For the part A of the study, full analysis set included all patients who received any amount of study treatment during the treatment period and had at least one post-baseline assessment during that period. Only patients with a value at both baseline and at the time point are included
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).
Outcome measures
| Measure |
Part A: Serelaxin (RLX030)
n=20 Participants
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
|
Part B: Serelaxin (RLX030)
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.
|
|---|---|---|
|
Change From Baseline of the Blood Flow for the Portal Vein (Study Part A (Serelaxin Treatment Group Only))
|
-0.091 L/min
Interval -0.204 to 0.023
|
—
|
SECONDARY outcome
Timeframe: Baseline, 120 min post infusionPopulation: For Part B of the study, full analysis set included all patients who received any amount of study treatment during the treatment period and had at least one post-baseline assessment during that period. Only patients with a value at both baseline and this time point are included.
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).
Outcome measures
| Measure |
Part A: Serelaxin (RLX030)
n=6 Participants
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
|
Part B: Serelaxin (RLX030)
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.
|
|---|---|---|
|
Change From Baseline of the Portal Vein Pressure (PVP) (Study Part B)
|
-3.7 mmHg
Interval -8.8 to 1.4
|
—
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Safety assessment happened on full analysis set which included all patients who received any amount of study treatment during the treatment period and had at least one post-Baseline assessment during that period.
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.
Outcome measures
| Measure |
Part A: Serelaxin (RLX030)
n=20 Participants
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
|
Part B: Serelaxin (RLX030)
n=6 Participants
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.
|
|---|---|---|
|
Number of Patients With Total Adverse Events, Serious Adverse and Death as Assessment of Safety and Tolerability of Serelaxin
Any adverse event
|
3 Patients
|
3 Patients
|
|
Number of Patients With Total Adverse Events, Serious Adverse and Death as Assessment of Safety and Tolerability of Serelaxin
Serious Adverse Events
|
1 Patients
|
2 Patients
|
|
Number of Patients With Total Adverse Events, Serious Adverse and Death as Assessment of Safety and Tolerability of Serelaxin
Death
|
0 Patients
|
0 Patients
|
Adverse Events
Part A: Serelaxin (RLX030)
Part A: Terlipressin Acetate
Part B: Serelaxin (RLX030)
Serious adverse events
| Measure |
Part A: Serelaxin (RLX030)
n=20 participants at risk
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
|
Part A: Terlipressin Acetate
n=20 participants at risk
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection.
|
Part B: Serelaxin (RLX030)
n=6 participants at risk
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.
|
|---|---|---|---|
|
Gastrointestinal disorders
Ascites
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/6
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.00%
0/20
|
0.00%
0/20
|
16.7%
1/6
|
|
Gastrointestinal disorders
Vomiting
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/6
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/6
|
|
Infections and infestations
Cellulitis
|
0.00%
0/20
|
0.00%
0/20
|
16.7%
1/6
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/6
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/20
|
0.00%
0/20
|
16.7%
1/6
|
Other adverse events
| Measure |
Part A: Serelaxin (RLX030)
n=20 participants at risk
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
|
Part A: Terlipressin Acetate
n=20 participants at risk
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection.
|
Part B: Serelaxin (RLX030)
n=6 participants at risk
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.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/20
|
20.0%
4/20
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/20
|
30.0%
6/20
|
0.00%
0/6
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/6
|
|
Infections and infestations
Cellulitis
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/6
|
|
Investigations
Electrocardiogram QT prolonged
|
5.0%
1/20
|
5.0%
1/20
|
33.3%
2/6
|
|
Investigations
Electrocardiogram T wave biphasic
|
0.00%
0/20
|
0.00%
0/20
|
16.7%
1/6
|
|
Nervous system disorders
Headache
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/6
|
|
Nervous system disorders
Syncope
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/6
|
|
Vascular disorders
Hypertension
|
0.00%
0/20
|
15.0%
3/20
|
0.00%
0/6
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER