Effect of Pioglitazone on Portal and Systemic Hemodynamics in Patients With Advanced Cirrhosis

Medical University of Vienna

Status and phase: Completed; Phase 4

Conditions: Portal Hypertension; Cirrhosis; Ascites

Treatments: Drug: Placebo; Drug: Pioglitazone

Study type: Interventional

Funder types: Other

Identifiers

NCT00570622

CIRRPIO

Details and patient eligibility

About

The purpose of this study is to investigate the response to pioglitazone on the hepatic venous pressure gradient and peripheral vascular responsiveness to vasoconstrictors in patients with advanced (Child´s Grade B or C) cirrhosis.

Full description

Cirrhotic liver disease is associated with portal hypertension including elevated portal pressure as well as hyperdynamic circulation and low peripheral vascular resistance. Endothelial nitric (NO) release is impaired in liver microvasculature, upregulation of eNOS activity in the cirrhotic liver may constitute a new strategy to correct the increased hepatic vascular tone in these patients. In contrary to this impaired endothelium-dependent relaxation (endothelial dysfunction) and NO deficiency in the cirrhotic liver, systemic and splanchnic circulation of cirrhotic patients is characterized by increased vascular tone and hyporesponsiveness to vasoconstrictors. In addition to increasing insulin sensitivity, thiazolidinediones, like pioglitazone decrease oxidative stress and inflammation and improve endothelial function. In a randomized controlled, parallel group double-blind study 20 Patients with advanced (Child´s Grade B or C) liver cirrhosis will receive pioglitazone or placebo for nine days. Portal hemodynamics and forearm blood flow response will be measured at baseline and after pioglitazone/placebo to investigate the effect of pioglitazone in these group of patients.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Cirrhosis, grade B or C (Child-Pugh score)

Exclusion criteria

• History of hypersensitivity to the trial drugs and contrast agent or to drugs with a similar chemical structure
• Treatment with vasoactive or non-steroidal anti-inflammatory drugs or systemic antibiotics one week before the study
• Exclusion criteria for hepatic hemodynamic investigation
• Cardiac, renal or respiratory failure
• Previous surgical or transjugular intrahepatic portosystemic shunt
• Insulin-dependent diabetes

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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20 participants in 2 patient groups, including a placebo group

1

Active Comparator group

Description:

Patients receive 60mg of pioglitazone once a day orally for 9 days

Treatment:

Drug: Pioglitazone

2

Placebo Comparator group

Description:

Patients receive Placebo orally once a day for 9 days

Treatment:

Drug: Placebo