Compensated Cirrhosis and Portal HypertensionPhase 2NCT01640964
An Exploratory Haemodynamic Study in Patients With Compensated Cirrhosis and Portal Hypertension
A Phase 2 study testing Terlipressin acetate and Serelaxin (RLX030) in people with Compensated Cirrhosis and Portal Hypertension, run by Novartis Pharmaceuticals at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Compensated Cirrhosis and Portal Hypertension
- What is being tested?
- Terlipressin acetate and Serelaxin (RLX030)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2013to Dec 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- Any contraindication to having an MRI scan
- Part B:
- -Contraindication to catheterization
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Exploratory Study to Investigate the Haemodynamic Effects of Serelaxin (RLX030) in Patients With Compensated Cirrhosis and Portal Hypertension
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).
- Being tested
- Terlipressin acetate, Serelaxin (RLX030)
- Keywords
- Portal hypertension, cirrhosis, TIPSS, MRI, MRA, portal pressure, portal pressure gradient
- Medical subject headings
- Hypertension, Portal, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Terlipressin acetateDrug
IV bolus injection
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
| Study group | Role | What they receive |
|---|---|---|
| Part A: Terlipressin acetate | Experimental | Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection. Receives: Drug: Terlipressin acetate |
| 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 Receives: Drug: Serelaxin (RLX030) |
| 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. Receives: Drug: Serelaxin (RLX030) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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).
Measured: Baseline, 120 min post-infusion start
Secondary outcomes (7)
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)
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2012 (estimated)
- Study startApr 2013
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Compensated Cirrhosis and Portal HypertensionStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01640964
- Sponsor's protocol ID
- CRLX030X2201
- Other IDs
- 2012-000236-26
- Status last verified
- Mar 2016
- First submitted
- 21 Jun 2012
- Last updated
- 15 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28245243
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study to Investigate the Haemodynamic Effects of Serelaxin (RLX030) in Patients With Compensated Cirrhosis and Portal Hypertension
- ClinicalTrials.gov ID
- NCT01640964
- Acronym / sponsor ID
- CRLX030X2201
- Keywords
- Portal hypertension, cirrhosis, TIPSS, MRI, MRA, portal pressure, portal pressure gradient
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 16 Jul 2012 (estimated)
- Results
- Posted 20 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A: Terlipressin acetate | Experimental | Drug: Terlipressin acetatePatients received terlipressin acetate 2 mg intravenous (IV) bolus injection. |
| Part A: Serelaxin (RLX030) | Experimental | Drug: 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) | Experimental | Drug: 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 Portal pressure gradient (PPG) data acquisition. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- -Cirrhosis of alcohol aetiology according to physician's assessment prior to screening.
- -Cirrhosis with clinical and/or endoscopic evidence of portal hypertension (e.g. oesophageal varices).
- Cirrhosis with TIPSS in situ and PPG>5mmHg.
- Fully functioning TIPSS without variceal filling as confirmed by portography.
Key exclusion criteria (9 listed)
- 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.
- BMI (weight[kg] / height[m^2]) > 40 kg/m^2.
- Any contraindication to having an MRI scan
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Terlipressin acetateIV bolus injection | Drug | Part A: Terlipressin acetate |
| Serelaxin (RLX030)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 | Drug | Part A: Serelaxin (RLX030), Part B Serelaxin (RLX030) |
Primary outcome
Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Serelaxin Treatment Group Only))
Time frame: Baseline, 120 min post serelaxin infusion
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)
Time frame: Baseline, 120 min post-infusion start
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).
7 secondary outcomes
Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Terlipressin Acetate Group Only))
Time frame: Baseline, 120 min post infusion
Change From Baseline of the Blood Flow for the Hepatic Artery (Study Part A (Serelaxin Treatment Group Only))
Time frame: Baseline, 120 min post-infusion
Change From Baseline of the Blood Flow for the Superior Mesenteric Artery (Study Part A (Serelaxin Treatment Group Only))
Time frame: Baseline, 120 min post-infusion
Change From Baseline of the Blood Flow for the Descending Thoracic Aorta (Study Part A (Serelaxin Treatment Group Only))
Time frame: Baseline, 120 min post-infusion
Change From Baseline of the Blood Flow for the Portal Vein (Study Part A (Serelaxin Treatment Group Only))
Time frame: Baseline, 120 min post-infusion
Change From Baseline of the Portal Vein Pressure (PVP) (Study Part B)
Time frame: Baseline, 120 min post infusion
Number of Patients With Total Adverse Events, Serious Adverse and Death as Assessment of Safety and Tolerability of Serelaxin
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28245243Snowdon 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.
Related trials for Compensated Cirrhosis and Portal Hypertension
RecruitingObservational study
The Value of Spleen Thickness and Spleen Diameter for Gastroesophageal Varices Diagnosis in Compensated Cirrhosis
Liver Cirrhosis, Gastroesophageal Varices
Not yet recruiting
Body-weight Reduction Effect on Portal Hypertension in Compensated Cirrhosis
Cirrhosis, Portal Hypertension
Not yet recruitingObservational study
Hepatic and Splenic Microcirculatory Perfusion for Ruling Out High-Risk Varices in Patients With Hepatitis B-Related Cirrhosis
Hepatitis B Virus Related Cirrhosis, Portal Hypertension Related to Cirrhosis
RecruitingObservational study
2D-shear Wave Spleen Elastography in Clinically Significant Portal Hypertension and High-risk Varices
Portal Hypertension Related to Cirrhosis, Esophageal Varices
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Terlipressin acetate and Serelaxin (RLX030) in people with Compensated Cirrhosis and Portal Hypertension, run by Novartis Pharmaceuticals at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Serelaxin Treatment Group Only)) (time frame: Baseline, 120 min post serelaxin infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01640964, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2016.