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Hemodynamic Effect of Simvastatin With Beta Blockers in Clinical Portal Hypertension (SIMBETA)

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ClinicalTrials.gov Identifier: NCT01282385
Recruitment Status : Unknown
Verified January 2011 by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau.
Recruitment status was:  Not yet recruiting
First Posted : January 25, 2011
Last Update Posted : January 25, 2011
Sponsor:
Information provided by:
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Brief Summary:

In the genesis and maintenance of PH associated with liver cirrhosis are two mechanisms that act synergistically. The first is an increase in hepatic vascular resistance, due in part to the disruption of liver structure inherent cirrhosis, and increased hepatic vascular tone is caused by the contraction of perivascular smooth muscle cells, myofibroblasts and hepatic stellate cells, which represents about 30% of global intrahepatic resistance and is believed to be due to the production Defective nitric oxide (NO). The second mechanism, which maintains and exacerbates HTP, is an increase of splanchnic blood flow caused by increased NO and other vasodilators at this level

In this regard, we believe that in patients with compensated liver cirrhosis, with portal pressure gradient> 10 mmHg, both acute responders betablockers test as non-responders, the association of antifibrotic drugs and / or vasodilators, chronic liver selective May be beneficial in the control of portal hypertension


Condition or disease Intervention/treatment Phase
Liver Cirrhosis Portal Hypertension. Drug: Simvastatin Drug: placebo Phase 4

Detailed Description:

This study was prospective, randomized, controlled, double blind, in which patients who met the inclusion criteria and give written consent to participate in the study underwent a baseline hemodynamic study to determine the portal pressure gradient (GPSH). During the event, will assess the acute response to intravenous administration of propranolol. It is considered good hemodynamic response to declining GPSH >20% from baseline or decrease to <12 mmHg. At the conclusion of the baseline hemodynamic study patients will be divided into 2 treatment groups:

a) patients responding to treatment with beta-blockers, in which she was treated with nadolol at doses of 40mg/24horas (increasing the dose every 2-3 days as tolerated, to a maximum of 240 mg / 24 hours. Subsequently randomized into two treatment arms, double-blind:

a.1: simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance.

a.2: placebo capsules with external characteristics similar to simvastatin.

b) non-responders to treatment with beta blockers, carvedilol receive treatment with an initial dose of 6.25 mg / 24 hours, may increase to 25mg/dia if good clinical tolerance (HR and BP monitoring) and analytical (renal function and electrolyte disturbances) . Subsequently randomized into two treatment arms, double-blind b.1: simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance.

b.2: placebo capsules with external characteristics similar to simvastatin.

In order to evaluate the long-term hemodynamic effect, patients will receive treatment for a month and hemodynamic study will be repeated to completion.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Hemodynamic Effect of the Combination of Simvastatin With Non-cardioselective Beta Blockers in Patients With Cirrhosis and Clinically Significant Portal Hypertension
Study Start Date : April 2011
Estimated Primary Completion Date : April 2014
Estimated Study Completion Date : April 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis
U.S. FDA Resources

Arm Intervention/treatment
Experimental: simvasatin

a) patients responding to treatment with beta-blockers, in which she was treated with nadolol Subsequently randomized into two treatment arms, double-blind:

a.1: simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance.

a.2: placebo capsules with external characteristics similar to simvastatin.

b) non-responders to treatment with beta blockers, receive treatment with carvedilol.Subsequently randomized into two treatment arms, double-blind

b.1: simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance.

b.2: placebo capsules with external characteristics similar to simvastatin.

Drug: Simvastatin
simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance
Placebo Comparator: placebo Drug: placebo
placebo capsules with external characteristics similar to simvastatin administrated each 24 hours.



Primary Outcome Measures :
  1. improvement of the hemodynamic response rate [ Time Frame: 1 month. ]
    The main objective is to assess whether, in patients with compensated cirrhosis, portal pressure greater than 10mmHg and esophageal varices at risk, the association of a liver selective vasodilator and simvastatin together with non-cardioselective beta blockers can improve the hemodynamic response rate.


Secondary Outcome Measures :
  1. Portal hypertension complications. [ Time Frame: 1 month ]
    Development of complications related to portal hypertension (gastrointestinal bleeding related to portal hypertension, ascites, hepatic encephalopathy).

  2. Adverse effects [ Time Frame: 1 month ]
    adverse effects related to medication



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Liver cirrhosis diagnosed by previous biopsy or by clinical, laboratory, ultrasound,
  • PPG> 10 mmHg,
  • Presence of large esophageal varices or small varices with red spots, varices of any size and Pugh C, and / or gastric fundic varices of any size, in a recent gastroscopy (<1 month)
  • Absence of previous episodes of gastrointestinal bleeding
  • Written informed consent.

Exclusion Criteria:

  • Age <18 and> 80 years;
  • Episode of variceal bleeding,
  • Thrombosis splenoportal axis,
  • Hepatocarcinoma,
  • Terminal liver failure (Child-Pugh scale> 13 points);
  • Any comorbidity involving a medical drugs and / or a life expectancy <12 months,
  • Severe chronic renal insufficiency (creatinine> 150 g / L),
  • Absolute contraindication or allergy treatment with statins to simvastatin;
  • Concomitant potent inhibitors of CYP3A4 (eg., itraconazole, ketoconazole, inhibitors of HIV protease, erythromycin, clarithromycin, telithromycin and nefazodone),
  • Pretreatment (<1 month) or other lipid-lowering with simvastatin,
  • Previous episodes rhabdomyolysis;
  • Contraindication to beta-blockers (COPD with bronchial hyperresponsiveness, aortic stenosis, AV block, intermittent claudication, severe psychosis, bronchial asthma),
  • Hypersensitivity to beta blockers,
  • Concomitant administration of potent inhibitors of cytochrome P-450 (quinidine, fluoxetine, paroxetine, and propafenone)
  • Active alcoholic hepatitis,
  • Refusal to participate in the study or the informed consent claim;
  • Pre-treatment with beta blockers or nitrates, or endoscopic treatment for varicose veins or portosystemic shunts;
  • Pregnancy and lactation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01282385


Contacts
Contact: Candido Villanueva, PHD 0034 5565917 cvillanueva@santpau.cat
Contact: Angela Puente, MD 00345565917 apuentesa@santpau.cat

Locations
Spain
Hospital de la Santa Creu i Sant Pau Not yet recruiting
Barcelona, Spain, 08025
Contact: Candido Villanueva, mPHD    0034935565917    cvillanueva@santpau.cat   
Contact: Angela Puente, PHD    0034935565917    apuentesa@santpau.cat   
Sub-Investigator: Angela Puente, PHD         
Principal Investigator: Candido Villanueva, mPHD         
Sponsors and Collaborators
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Investigators
Principal Investigator: Candido Villanueva, MD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Publications of Results:
Other Publications:
Responsible Party: Candido Villanueva, Hospital de la Santa Creu i Sant Pau
ClinicalTrials.gov Identifier: NCT01282385     History of Changes
Other Study ID Numbers: IIBSP-SIM-2010-04
First Posted: January 25, 2011    Key Record Dates
Last Update Posted: January 25, 2011
Last Verified: January 2011

Additional relevant MeSH terms:
Hypertension
Fibrosis
Liver Cirrhosis
Hypertension, Portal
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Liver Diseases
Digestive System Diseases
Simvastatin
Adrenergic beta-Antagonists
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs