Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06630572
Status:
TERMINATED
Last Update Posted:
None
First Post:
2018-01-18
Brief Title:
Rifaximin in Cirrhosis Effects on Endotoxin and Haemostatic Indexes
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Rifaximin Blunted Higher Levels of Endotoxin in Cirrhosis Patients a Randomized Double Blind Short Term Interventional Trial
Status:
TERMINATED
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Because drug is expired
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Rifaximin is an antibiotic that acts locally in the gastrointestinal tract with a broad spectrum of antibacterial activity The efficacy of rifaximin is well documented in the prevention of acute hepatic encephalopathy There is no evidence on its benefit to modulate hypercoagulative state in cirrhotic patient
To assess the effect of a short-term treatment with rifaximin on systemic levels of intestinal endotoxin and on platelet and coagulation markers in patients with decompensated cirrhosis the study has been planned
To assess the effect of a short-term treatment with rifaximin on systemic levels of intestinal endotoxin and on platelet and coagulation markers in patients with decompensated cirrhosis the study has been planned
Detailed Description:
The term coagulopathy has been coined because of impaired clotting activation detected by laboratory tests in association with deterioration of liver function the frequent coexistence of hyperfibrinolysis low platelet count and platelet dysfunction reinforced the concept that coagulopathy is associated with cirrhosis
This concept has been recently challenged for several reasons The prolongation of global tests of clotting activation does not actually reflect hemostatic changes in vivo and maybe a laboratory artefact In addition cirrhotic patients actually disclose a tendency to a hypercoagulation state which seems to be related to endotoxemia and may be detected in both peripheral and portal circulation and to an increased platelet activation
Bacterial lipopolysaccharide LPS endotoxin is elevated in cirrhosis particularly in decompensated cirrhosis with a mechanism related to an enhanced gut permeability and ensuing translocation of LPS in the peripheral circulation Recent data demonstrated that cirrhosis is associated with a low-grade endotoxemia which is more evident in Child-Pugh classes B and C Of note LPS significantly correlated with sCD40L and sPs suggesting a role for LPS in eliciting platelet activation
It is difficult to believe that under these circumstances patients with cirrhosis are at high risk of bleeding thus apart from gastrointestinal tract bleeding which is independent of changes of the clotting system spontaneous bleeding in cirrhosis is rare Conversely in vivo data reporting the existence of platelet and clotting activation may explain the increased risk for thrombosis overall in portal circulation This opens a new and interesting scenario as portal vein thrombosis which may occur in approximately 20 of cirrhotic patients should be treated with antithrombotic drugs httpsclinicaltrialsgovct2showNCT01470547 However planning trials with anticoagulants in cirrhosis will be very difficult because the persistent concept of coagulopathy in cirrhosis is likely to be a barrier against the use of anticoagulants
Interventional trials to modulate low-grade endotoxemia are warranted to assess if this therapeutic approach may reduce the risk of thrombosis in cirrhosis
In a small cohort of cirrhotic a previous study demonstrated that administration of non-absorbable antibiotic reduces thrombin generation coincidentally with serum LPS reduction suggesting a role for LPS as trigger of clotting activation No data were provided however on the effect of this treatment on platelet activation or on the duration of clotting system inhibition
Rifaximin is an antibiotic that acts locally in the gastrointestinal tract with a broad spectrum of antibacterial activity The efficacy of rifaximin is well documented in the prevention of acute hepatic encephalopathy HE It is recommended as a first-line therapy for HE and was recently approved for the prevention of HE in high-risk populations More recently clinical trials have been performed to evaluate the effect of this drug on the prophylaxis of spontaneous bacterial peritonitis SBP and other cirrhosis-related complications Although these studies demonstrated excellent prospects for the clinical application of rifaximin there is no evidence on its benefit to modulate hypercoagulative state in the cirrhotic patient
Study objective to assess the effect of a short-term 14 days treatment with rifaximin 1100 mgdie on systemic levels of intestinal endotoxin and on platelet and coagulation markers in patients with decompensated cirrhosis
This concept has been recently challenged for several reasons The prolongation of global tests of clotting activation does not actually reflect hemostatic changes in vivo and maybe a laboratory artefact In addition cirrhotic patients actually disclose a tendency to a hypercoagulation state which seems to be related to endotoxemia and may be detected in both peripheral and portal circulation and to an increased platelet activation
Bacterial lipopolysaccharide LPS endotoxin is elevated in cirrhosis particularly in decompensated cirrhosis with a mechanism related to an enhanced gut permeability and ensuing translocation of LPS in the peripheral circulation Recent data demonstrated that cirrhosis is associated with a low-grade endotoxemia which is more evident in Child-Pugh classes B and C Of note LPS significantly correlated with sCD40L and sPs suggesting a role for LPS in eliciting platelet activation
It is difficult to believe that under these circumstances patients with cirrhosis are at high risk of bleeding thus apart from gastrointestinal tract bleeding which is independent of changes of the clotting system spontaneous bleeding in cirrhosis is rare Conversely in vivo data reporting the existence of platelet and clotting activation may explain the increased risk for thrombosis overall in portal circulation This opens a new and interesting scenario as portal vein thrombosis which may occur in approximately 20 of cirrhotic patients should be treated with antithrombotic drugs httpsclinicaltrialsgovct2showNCT01470547 However planning trials with anticoagulants in cirrhosis will be very difficult because the persistent concept of coagulopathy in cirrhosis is likely to be a barrier against the use of anticoagulants
Interventional trials to modulate low-grade endotoxemia are warranted to assess if this therapeutic approach may reduce the risk of thrombosis in cirrhosis
In a small cohort of cirrhotic a previous study demonstrated that administration of non-absorbable antibiotic reduces thrombin generation coincidentally with serum LPS reduction suggesting a role for LPS as trigger of clotting activation No data were provided however on the effect of this treatment on platelet activation or on the duration of clotting system inhibition
Rifaximin is an antibiotic that acts locally in the gastrointestinal tract with a broad spectrum of antibacterial activity The efficacy of rifaximin is well documented in the prevention of acute hepatic encephalopathy HE It is recommended as a first-line therapy for HE and was recently approved for the prevention of HE in high-risk populations More recently clinical trials have been performed to evaluate the effect of this drug on the prophylaxis of spontaneous bacterial peritonitis SBP and other cirrhosis-related complications Although these studies demonstrated excellent prospects for the clinical application of rifaximin there is no evidence on its benefit to modulate hypercoagulative state in the cirrhotic patient
Study objective to assess the effect of a short-term 14 days treatment with rifaximin 1100 mgdie on systemic levels of intestinal endotoxin and on platelet and coagulation markers in patients with decompensated cirrhosis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None