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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-000236-26 | EudraCT Number |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Terlipressin acetate | Experimental | Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection. |
|
| Part A: Serelaxin (RLX030) | Experimental | 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) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Terlipressin acetate | Drug | IV bolus injection |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | Baseline, 120 min post serelaxin infusion |
| 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). | Baseline, 120 min post-infusion start |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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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:
Exclusion Criteria:
Study Parts A and B:
Part A:
Part B:
-Contraindication to catheterization
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Edinburgh | EH16 4TJ | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28245243 | Derived | 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. |
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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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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: Terlipressin Acetate | Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection. |
| FG001 | 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 |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A: Terlipressin Acetate | Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection. |
| BG001 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | 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. | Posted | Mean | 95% Confidence Interval | L/min | Baseline, 120 min post serelaxin infusion |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ascites | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | trialandresults.registries@novartis.com |
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| ID | Term |
|---|---|
| D006975 | Hypertension, Portal |
| D005355 | Fibrosis |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000077585 | Terlipressin |
| ID | Term |
|---|---|
| D008236 | Lypressin |
| D014667 | Vasopressins |
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
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| Serelaxin (RLX030) |
| Drug |
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 |
|
| Baseline, 120 min post infusion |
| 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). | Baseline, 120 min post-infusion |
| 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). | Baseline, 120 min post-infusion |
| 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). | Baseline, 120 min post-infusion |
| 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). | Baseline, 120 min post-infusion |
| 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). | Baseline, 120 min post 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. | 4 weeks |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Patients |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Primary | 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). | 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. | Posted | Mean | 95% Confidence Interval | mmHg | Baseline, 120 min post-infusion start |
|
|
|
| Secondary | 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) | 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. | Posted | Mean | 95% Confidence Interval | L/min | Baseline, 120 min post infusion |
|
|
|
| Secondary | 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). | 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 | Posted | Mean | 95% Confidence Interval | L/min | Baseline, 120 min post-infusion |
|
|
|
| Secondary | 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). | 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 | Posted | Mean | 95% Confidence Interval | L/min | Baseline, 120 min post-infusion |
|
|
|
| Secondary | 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). | 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 | Posted | Mean | 95% Confidence Interval | L/min | Baseline, 120 min post-infusion |
|
|
|
| Secondary | 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). | 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 | Posted | Mean | 95% Confidence Interval | L/min | Baseline, 120 min post-infusion |
|
|
|
| Secondary | 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). | 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. | Posted | Mean | 95% Confidence Interval | mmHg | Baseline, 120 min post infusion |
|
|
|
| Secondary | 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. | 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. | Posted | Number | Patients | 4 weeks |
|
|
|
| 1 |
| 20 |
| 2 |
| 20 |
| EG001 | Part A: Terlipressin Acetate | Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection. | 1 | 20 | 11 | 20 |
| EG002 | 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. | 2 | 6 | 2 | 6 |
| Oesophageal varices haemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Alcohol poisoning | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Hepatic encephalopathy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA | Systematic Assessment |
|
| Electrocardiogram T wave biphasic | Investigations | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
|
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.
| D036361 |
| Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| Death |
|