A Phase 4 interventional study of Rifaximin and Placebo in Liver Cirrhosis, Coagulation Disorder and Platelet Disorder, sponsored by University of Roma La Sapienza. Terminated at 1 site in Italy. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-10-08.
Sponsored by University of Roma La Sapienza · Phase 4, Interventional, and Treatment
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.
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 (https://clinicaltrials.gov/ct2/show/NCT01470547). 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 mg/die) on systemic levels of intestinal endotoxin and on platelet and coagulation markers in patients with decompensated cirrhosis.
1,298 studies on the registry are indexed under Liver Cirrhosis; 338 are open to participants now.
This study's enrollment of 20 is below the median of 78 across 739 interventional studies indexed under Liver Cirrhosis.
Browse Liver Cirrhosis studies →University of Roma La Sapienza is the lead sponsor of 398 studies on the registry; 56 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Rifaximin (1100 mg/die) - 550 b.i.d.
Drug: Rifaximin
Placebo - b.i.d.
Drug: Placebo
Patients randomized to receive Rifaximin for 14 days
Patients randomized to receive Placebo for 14 days
Decrease in serum endotoxemia after 14-day treatment with Rifaximin.
Significant decrease (-20%) in serum bacterial LPS (endotoxemia) after 14-day treatment with Rifaximin 550 mg b.i.d respect to the control group as well as after 30 and 60 days from the end of the treatment.
Time frame: 14, 30, 60 Days
Impact of serum changes of LPS on coagulation and/or platelet indexes
Significant correlation between change in serum LPS and thrombin generation and/or platelet activation indexes in both groups to support the role of LPS as trigger of clotting activation and platelet activation.
Time frame: 14, 30, 60 Days
Clinical Failure
Proportion of patients with clinical failure.
Time frame: 14, 30, 60 Days
Safety and tolerability: Number of participants with adverse events as a measure of safety and tolerability
Number of participants with adverse events as a measure of safety and tolerability
Time frame: 14, 30, 60 Days
Platelet activation
Evaluation of soluble markers of platelet activation \[Flow cytometric analysis and ELISA\]
Time frame: 14, 30, 60 Days
Platelet- leukocyte aggregation
Evaluation of platelet-leukocyte aggregates by Flow cytometric analysis
Time frame: 14, 30, 60 Days
Platelet turnover
Determination of platelet indices indicative of elevated platelet turnover.
Time frame: 14, 30, 60 Days
Gut microbiota
Evaluation of intestinal barrier permeability, by ELISA for LPS, marker of gut permeability.
Time frame: 14, 30, 60 Days
Neutrophil extracellular traps (NETs)
Soluble markers of neutrophil extracellular trap (NET) in circulation.
Time frame: 14, 30, 60 Days
Gut microbiota
Evaluation of intestinal barrier permeability, by ELISA for Zonulin, marker of gut permeability.
Time frame: 14, 30, 60 Days
Plan to share: No
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Studies of the drug tested here: Rifaximin
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