Rifaximin in Cirrhosis: Effects on Endotoxin and Haemostatic Indexes

NCT06630572 | Terminated Phase 4 DMC

• 1 other identifier: EudraCT 2017-000488-34
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Cirrhosis; Coagulation Disorder; Platelet Disorder; Endotoxemia

Keywords

Rifaximin; Liver Cirrhosis; Endotoxin; Platelet function

Outcome Measures

Primary Outcomes (1)

• 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.

  14, 30, 60 Days

Secondary Outcomes (3)

• Impact of serum changes of LPS on coagulation and/or platelet indexes

  14, 30, 60 Days

• Clinical Failure

  14, 30, 60 Days

• Safety and tolerability: Number of participants with adverse events as a measure of safety and tolerability

  14, 30, 60 Days

Other Outcomes (6)

• Platelet activation

  14, 30, 60 Days

• Platelet- leukocyte aggregation

  14, 30, 60 Days

• Platelet turnover

  14, 30, 60 Days

Study Arms (2)

TREATMENT

EXPERIMENTAL

Rifaximin (1100 mg/die) - 550 b.i.d.

Drug: Rifaximin

PLACEBO

PLACEBO COMPARATOR

Placebo - b.i.d.

Drug: Placebo

Interventions

Rifaximin DRUG

Patients randomized to receive Rifaximin for 14 days

TREATMENT

Placebo DRUG

Patients randomized to receive Placebo for 14 days

PLACEBO

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18-75 years
• Patients of Child-Pugh grade B or C (decompensated liver cirrhosis, as confirmed by clinical symptoms and signs, laboratory results, ultrasound and spiral computed tomography)

You may not qualify if:

• Presence of overt infection or sepsis
• Treatment with systemic or non-absorbable antibiotic, aspirin or other non-steroidal anti-inflammatory drugs, antidepressant drugs in the previous 30 days
• Recent need of transfusion of platelets or plasma
• Presence of extra-hepatic malignancy
• Active alcohol intake in the last 6 months
• Pregnancy or breast feeding
• Presence of overt HE, GI haemorrhage, SBP or other concurrent infections during the previous one month
• Human immunodeficiency virus (HIV) infection
• Chronic renal and/or respiratory insufficiency
• Severe heart disease
• Allergy to rifaximin
• Active post-viral hepatitis requiring or on direct-acting antiviral (DAA) agents
• Previous or active intestinal obstruction.

Sponsors & Collaborators

• University of Roma La Sapienza: lead
• Azienda Policlinico Umberto I: collaborator

Study Sites (1)

Sapienza University of Rome - Policlinico Umberto I Roma

Rome, 00161, Italy

Location

Related Publications (9)

• Violi F, Ferro D. Clotting activation and hyperfibrinolysis in cirrhosis: implication for bleeding and thrombosis. Semin Thromb Hemost. 2013 Jun;39(4):426-33. doi: 10.1055/s-0033-1334144. Epub 2013 Mar 13.

  PMID: 23487343 BACKGROUND

• Violi F, Ferro D, Basili S, Lionetti R, Rossi E, Merli M, Riggio O, Bezzi M, Capocaccia L. Ongoing prothrombotic state in the portal circulation of cirrhotic patients. Thromb Haemost. 1997 Jan;77(1):44-7.

  PMID: 9031447 BACKGROUND

• Nolan JP. The role of intestinal endotoxin in liver injury: a long and evolving history. Hepatology. 2010 Nov;52(5):1829-35. doi: 10.1002/hep.23917.

  PMID: 20890945 BACKGROUND

• Raparelli V, Basili S, Carnevale R, Napoleone L, Del Ben M, Nocella C, Bartimoccia S, Lucidi C, Talerico G, Riggio O, Violi F. Low-grade endotoxemia and platelet activation in cirrhosis. Hepatology. 2017 Feb;65(2):571-581. doi: 10.1002/hep.28853. Epub 2016 Nov 5.

  PMID: 27641757 BACKGROUND

• Violi F, Basili S, Raparelli V, Chowdary P, Gatt A, Burroughs AK. Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction? J Hepatol. 2011 Dec;55(6):1415-27. doi: 10.1016/j.jhep.2011.06.008. Epub 2011 Jun 28.

  PMID: 21718668 BACKGROUND

• Ferro D, Angelico F, Caldwell SH, Violi F. Bleeding and thrombosis in cirrhotic patients: what really matters? Dig Liver Dis. 2012 Apr;44(4):275-9. doi: 10.1016/j.dld.2011.10.016. Epub 2011 Nov 25.

  PMID: 22119620 BACKGROUND

• Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, Sigal S, Sheikh MY, Beavers K, Frederick T, Teperman L, Hillebrand D, Huang S, Merchant K, Shaw A, Bortey E, Forbes WP. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010 Mar 25;362(12):1071-81. doi: 10.1056/NEJMoa0907893.

  PMID: 20335583 BACKGROUND

• Rivkin A, Gim S. Rifaximin: new therapeutic indication and future directions. Clin Ther. 2011 Jul;33(7):812-27. doi: 10.1016/j.clinthera.2011.06.007. Epub 2011 Jul 7.

  PMID: 21741091 BACKGROUND

• Danulescu RM, Ciobica A, Stanciu C, Trifan A. The role of rifaximine in the prevention of the spontaneous bacterial peritonitis. Rev Med Chir Soc Med Nat Iasi. 2013 Apr-Jun;117(2):315-20.

  PMID: 24340510 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis; Hemostatic Disorders; Blood Platelet Disorders; Endotoxemia

Interventions

Rifaximin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Bacteremia; Sepsis; Infections; Toxemia; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Stefania BASILI, Prof.

  SAPIENZA UNIVERSITY- Department of Translational and Precision Medicine

  STUDY CHAIR

• Oliviero Riggio, Prof.

  SAPIENZA UNIVERSITY- Department of Translational and Precision Medicine

  PRINCIPAL INVESTIGATOR

• Manuela Merli, Prof.

  SAPIENZA UNIVERSITY- Department of Translational and Precision Medicine

  PRINCIPAL INVESTIGATOR

• Lucia Stefanini, Prof.

  SAPIENZA UNIVERSITY- Department of Translational and Precision Medicine

  PRINCIPAL INVESTIGATOR

• Roberto Carnevale, Prof.

  SAPIENZA UNIVERSITY

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Randomized, placebo control, double-blind trial.

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: October 8, 2024
• Study Start: April 3, 2021
• Primary Completion: April 3, 2022
• Study Completion: August 1, 2024
• Last Updated: October 8, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)