NCT05187715

Brief Summary

Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of end-stage liver disease that is characterized by decreased arterial oxygenation caused by intrapulmonary vascular dilatation. Due to the different diagnostic criteria used in different studies, its prevalence ranges from 4% to 47% in patients with cirrhosis. Main underlaying pathogensis for HPS being activation of macrophages which are responsible for iNOS, PDGF and VEGF release contributing to development of intrapulmonary vascular dilatation(IPVD) , and neoangiogenesis leading to anatomical shunt resulting decreased oxygenation. Sphingosine 1 phosphate (S1P) is an essential compound produced and secreted by endothelial cells, platelets and RBC's. S1P prevents adhesion, transmigration and release of inflammatory mediators from macrophages. S1P levels are decreased in cirrhotics. Simvastatin, a HMG CoA inhibitor has many pleotropic effects, Of which one is by agonizing the S1P response and improving oxygenation in HPS patients. Simvastatin at a optimal dose of 40mg/day for 6months. Pre and post simvastatin treatment related oxygenation changes and concurrently its effect on liver fibrosis will be evaluated.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
45

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Feb 2022

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 8, 2021

Completed
1 month until next milestone

First Posted

Study publicly available on registry

January 12, 2022

Completed
2 months until next milestone

Study Start

First participant enrolled

February 26, 2022

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2023

Completed
Last Updated

March 15, 2022

Status Verified

October 1, 2021

Enrollment Period

1.6 years

First QC Date

December 8, 2021

Last Update Submit

February 28, 2022

Conditions

Liver Cirrhosis

Outcome Measures

Primary Outcomes (1)

  • Achievement of complete response by the end of 6 months

    6 months

Secondary Outcomes (4)

  • Transplant free survival

    3 months

  • Transplant free survival

    6 months

  • Severity of Liver Disease

    6 months

  • Development of serious adverse effects leading to withdrawal of the drug or death from any cause.

    2 years

Study Arms (2)

Simvastatin with Standard Medical Treatment

EXPERIMENTAL

Simvastatin 40mg OD plus standard treatment plus standard treatment (excluding Pentoxiphylline)

Drug: Simvastatin 40mgOther: Standard medical Treatment

Placebo with Standard Medical Treatment

ACTIVE COMPARATOR

Matched placebo plus standard treatment (excluding Pentoxiphylline)

Other: PlaceboOther: Standard medical Treatment

Interventions

Simvastatin 40mgDRUG

Simvastatin 40mg OD

Simvastatin with Standard Medical Treatment
PlaceboOTHER

Placebo

Placebo with Standard Medical Treatment
Standard medical TreatmentOTHER

Standard medical Treatment eccluding pentoxiphylline

Placebo with Standard Medical TreatmentSimvastatin with Standard Medical Treatment

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosed case of Hepato-pulmonary syndrome AaPO2 \> 15 mm Hg on standing room air arterial blood gas (ABG). PaO2\<80 mmHg for clinical HPS between 18-70 years of years
  • Child A/B cirrhosis, Child C with CTP score of =/\<10
  • Patient with no liver transplant option

You may not qualify if:

  • Child-C cirrhosis CTP \>10
  • Very Severe HPS
  • Acute-on-chronic liver failure
  • Thrombosis of splenoportal axis
  • Hepatocellular carcinoma
  • Renal dysfunction
  • Patients intolerant to beta blockers (history of hypotension or bradycardia)
  • Contraindication for beta-blockers (history of chronic obstructive pulmonary disease, atrioventricular block)
  • Pregnant females
  • Refusal to participate in the study
  • Hepatic Hydrothorax

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesFibrosisPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

LovastatinNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Central Study Contacts

Dr Akhil Deshmukh, MD

CONTACT

01146300000akhildeshmukh52@gmail.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 8, 2021

First Posted

January 12, 2022

Study Start

February 26, 2022

Primary Completion

October 1, 2023

Study Completion

October 1, 2023

Last Updated

March 15, 2022

Record last verified: 2021-10

Locations

IN(1)