Liver CirrhosisPhase 2/3NCT01456286
Randomized Controlled Trial to Assess the Effects of Sapropterin on Hepatic and Systemic Hemodynamics in Patients With Liver Cirrhosis and Portal Hypertension
A Phase 2/3 study testing sapropterin in people with Liver Cirrhosis and Portal Hypertension, run by Fundacion Clinic per a la Recerca Biomédica at 2 sites in Spain.
Trial summary
The purpose of this study is to determine whether sapropterin (an oral analogue of tetrahydrobiopterin) could have a role in the treatment of portal hypertension secondary to liver cirrhosis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Cirrhosis, Portal Hypertension
- What is being tested?
- sapropterin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 2 sitesSpain
- Study dates
- Oct 2011to Oct 2013
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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
- Liver cirrhosis of any etiology diagnosed by biopsy or by clinical-imaging data
- Male or female patients between 18-75 years old in whom hepatic vein catheterization is indicated.
- Clinically significant portal hypertension defined by a HVPG ≥ 10 mmHg.
- Signed informed consent.
Who cannot join
- End-stage liver failure defined by one of the following: Prothrombin activity < 40% and/or Bilirubin > 5 mg/dl.
- Pregnancy or breastfeeding.
- Concomitant beginning of non-selective beta-blockers (propranolol, nadolol) during the administration of sapropterin. Beta-blockers are not exclusion criteria if they are on stable doses in the previous 6 weeks.
- Treatment with carvedilol or nitrates.
- Previous TIPS or derivative shunt.
- Hepatocellular carcinoma exceeding Milan criteria.
Show all 11Show fewer
- Spontaneous bacterial peritonitis or any active infection when entering in the study.
- Portal vein thrombosis or cavernomatosis at ultrasound.
- Chronic heart failure, respiratory failure or chronic renal failure (Creatinine >2 mg/dl).
- Previous convulsions or epilepsy.
- Hypersensibility to sapropterin or any of its excipients.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Hospital Clínic de Barcelona
Barcelona, Barcelona, 08036
Hospital Ramón y Cajal
Madrid, Madrid Community, 28034
About this study
Official title: Randomized Trial, Masked, and Placebo Controlled to Assess the Effects of Sapropterin on Hepatic and Systemic Hemodynamics in Patients With Liver Cirrhosis and Portal Hypertension
The purpose of this study is to determine whether sapropterin (an oral analogue of tetrahydrobiopterin) could have a role in the treatment of portal hypertension secondary to liver cirrhosis. Sapropterin or placebo will be given for two weeks in patients with liver cirrhosis and clinically significant portal hypertension. Systemic and hepatic hemodynamics studies will be performed at baseline and after the intervention to assess the effect of sapropterin.
Read the detailed description
Portal hypertension and its complications (variceal bleeding, encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome) are the main cause of death and liver transplantation in patients with cirrhosis. Diminishing portal hypertension by drugs (beta-blockers) is associated with a protection in the development of complications from portal hypertension. For this reason it is important to investigate and develop drugs that can reduce the portal pressure in liver cirrhosis. Tetrahydrobiopterin has been shown to decrease portal pressure in animal models of cirrhosis by improving intrahepatic resistance and by increasing nitric oxide bioavailability (eNOS co-factor). These effects were not associated to deleterious effects on systemic hemodynamics.
This study aims to test if sapropterin (an oral analogue of tetrahydrobiopterin) can play a role in the management of portal hypertension. For this, patients with liver cirrhosis and clinically significant portal hypertension will be randomized to receive sapropterin or placebo for two weeks. Patients will undergo an hepatic vein catheterization to asses the hepatic venous pressure gradient (HVPG), and those having and HVPG of 10 mmHg or higher will be randomized to receive sapropterin or placebo. Swan-Ganz catheterization, systemic measurements, and hepatic blood flow by indocyanine green method will also be performed. Patients will receive sapropterin or placebo for two weeks at a dosage of 5 mg/kg/d in the first week, increasing to 10 mg/kg/d in the second week if there are no adverse events or intolerance. A second systemic and hepatic hemodynamic study will be performed after 2 weeks of treatment to assess changes.
Changes in laboratory tests, liver function (Child-Pugh and MELD scores), endothelial dysfunction and oxidative stress markers (Von Willebrand Factor, Malondialdehyde) will be monitored during the study. As sapropterin has been never evaluated in cirrhotic patients, tolerance and adverse effects related to the medication will be registered.
The study will be stratified according to previous beta-blocker therapy (receiving or not receiving beta-blockers).
- Conditions
- Liver Cirrhosis, Portal Hypertension
- Being tested
- sapropterin
- Medical subject headings
- Liver Cirrhosis, Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sapropterinDrug
two weeks of treatment: 5 mg/kg per day during first week 10 mg/kg per day during second week
| Study group | Role | What they receive |
|---|---|---|
| Sapropterin | Experimental | 5 mg/kg daily first week; 10 mg/kg daily second week of treatment Receives: Drug: sapropterin |
| placebo | Placebo comparator | Not described Receives: Drug: sapropterin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Hepatic Venous Pressure Gradient
Changes in portal pressure gradient as measured by hepatic vein catheterization, induced by 2 week treatment with sapropterin/placebo
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion Clinic per a la Recerca Biomédica
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sara Varea, Fundacion Clinic per a la Recerca Biomédica
- Investigators
- Juan C García-Pagán, MD phD, Principal investigator, Hospital Clínic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01456286
- Sponsor's protocol ID
- TEHYLIC
- Status last verified
- Oct 2013
- First submitted
- 17 Oct 2011
- Last updated
- 7 Oct 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial, Masked, and Placebo Controlled to Assess the Effects of Sapropterin on Hepatic and Systemic Hemodynamics in Patients With Liver Cirrhosis and Portal Hypertension
- ClinicalTrials.gov ID
- NCT01456286
- Acronym / sponsor ID
- TEHYLIC
- Conditions
- Liver Cirrhosis, Portal Hypertension
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Fundacion Clinic per a la Recerca BiomédicaUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 20 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether sapropterin (an oral analogue of tetrahydrobiopterin) could have a role in the treatment of portal hypertension secondary to liver cirrhosis. Sapropterin or placebo will be given for two weeks in patients with liver cirrhosis and clinically significant portal hypertension. Systemic and hepatic hemodynamics studies will be performed at baseline and after the intervention to assess the effect of sapropterin.
Detailed description
Portal hypertension and its complications (variceal bleeding, encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome) are the main cause of death and liver transplantation in patients with cirrhosis. Diminishing portal hypertension by drugs (beta-blockers) is associated with a protection in the development of complications from portal hypertension. For this reason it is important to investigate and develop drugs that can reduce the portal pressure in liver cirrhosis. Tetrahydrobiopterin has been shown to decrease portal pressure in animal models of cirrhosis by improving intrahepatic resistance and by increasing nitric oxide bioavailability (eNOS co-factor). These effects were not associated to deleterious effects on systemic hemodynamics.
This study aims to test if sapropterin (an oral analogue of tetrahydrobiopterin) can play a role in the management of portal hypertension. For this, patients with liver cirrhosis and clinically significant portal hypertension will be randomized to receive sapropterin or placebo for two weeks. Patients will undergo an hepatic vein catheterization to asses the hepatic venous pressure gradient (HVPG), and those having and HVPG of 10 mmHg or higher will be randomized to receive sapropterin or placebo. Swan-Ganz catheterization, systemic measurements, and hepatic blood flow by indocyanine green method will also be performed. Patients will receive sapropterin or placebo for two weeks at a dosage of 5 mg/kg/d in the first week, increasing to 10 mg/kg/d in the second week if there are no adverse events or intolerance. A second systemic and hepatic hemodynamic study will be performed after 2 weeks of treatment to assess changes.
Changes in laboratory tests, liver function (Child-Pugh and MELD scores), endothelial dysfunction and oxidative stress markers (Von Willebrand Factor, Malondialdehyde) will be monitored during the study. As sapropterin has been never evaluated in cirrhotic patients, tolerance and adverse effects related to the medication will be registered.
The study will be stratified according to previous beta-blocker therapy (receiving or not receiving beta-blockers).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sapropterin | Experimental | Drug: sapropterin5 mg/kg daily first week; 10 mg/kg daily second week of treatment |
| placebo | Placebo comparator | Drug: sapropterin |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Liver cirrhosis of any etiology diagnosed by biopsy or by clinical-imaging data
- Male or female patients between 18-75 years old in whom hepatic vein catheterization is indicated.
- Clinically significant portal hypertension defined by a HVPG ≥ 10 mmHg.
- Signed informed consent.
Key exclusion criteria (11 listed)
- End-stage liver failure defined by one of the following: Prothrombin activity < 40% and/or Bilirubin > 5 mg/dl.
- Pregnancy or breastfeeding.
- Concomitant beginning of non-selective beta-blockers (propranolol, nadolol) during the administration of sapropterin. Beta-blockers are not exclusion criteria if they are on stable doses in the previous 6 weeks.
- Treatment with carvedilol or nitrates.
- Previous TIPS or derivative shunt.
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 |
|---|---|---|
| sapropterintwo weeks of treatment: 5 mg/kg per day during first week 10 mg/kg per day during second week | Drug | Sapropterin, placebo |
Primary outcome
Changes in Hepatic Venous Pressure Gradient
Time frame: 2 weeks
Changes in portal pressure gradient as measured by hepatic vein catheterization, induced by 2 week treatment with sapropterin/placebo
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2013.
Related trials for Liver Cirrhosis
RecruitingObservational study
Effectiveness and Clinical Outcomes of Long-term Bulevirtide Monotherapy in Patients With HDV-related Compensated Cirrhosis
Hepatitis D
Recruiting
Optimal Treatment Strategy for Spontaneous Bacterial Peritonitis
Spontaneous Bacterial Peritonitis, Paracentesis
RecruitingObservational study
The Value of Spleen Thickness and Spleen Diameter for Gastroesophageal Varices Diagnosis in Compensated Cirrhosis
Liver Cirrhosis, Gastroesophageal Varices
Recruiting
CirrhosisRx CDS System
Cirrhosis, Decision Support Systems, Clinical
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
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.
Juan C García-Pagán, MD phD principal investigator
Hospital Clínic of Barcelona
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing sapropterin in people with Liver Cirrhosis and Portal Hypertension, run by Fundacion Clinic per a la Recerca Biomédica at 2 sites in Spain.
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 4 inclusion and 11 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 7 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Changes in Hepatic Venous Pressure Gradient (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Oct 2013.