Liver CirrhosisPhase 4NCT07459972
Clinical Evaluation of Simcyp-Guided Simvastatin Dosing in Patients With Liver Cirrhosis
A Phase 4 study testing Simvastatin 15 mg and Simvastatin 5 mg in people with Liver Cirrhosis and Portal Hypertension Related to Cirrhosis, run by Kafrelsheikh University at 1 site in Egypt.
Trial summary
This prospective open-label parallel pilot clinical study evaluated the efficacy and safety of physiologically based pharmacokinetic (PBPK)-guided simvastatin dosing in Child-Pugh A and B cirrhotic patients with portal hypertension over a 3-month period. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Cirrhosis, Portal Hypertension Related to Cirrhosis
- What is being tested?
- Simvastatin 15 mg and Simvastatin 5 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteEgypt
- Study dates
- 15 Mar 2024to 15 Jun 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients aged ≥ 18 years
- Confirmed diagnosis of liver cirrhosis (clinical, laboratory, or imaging evidence)
- Evidence of portal hypertension (clinical findings and/or Doppler ultrasound measurements)
- No previous history of variceal bleeding
- Child-Pugh class A or B
Who cannot join
- Active hepatocellular carcinoma
- Severe renal impairment (eGFR < 30 mL/min/1.73 m²)
- Baseline creatine kinase (CK) > 3 × upper limit of normal
- Known hypersensitivity to simvastatin
- Current therapy with strong CYP3A4 inhibitors
- Any active malignancy in the last 2 years
- Pregnancy or lactation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dose Prediction for Statins and Anticoagulant Medications in Cirrhotic Patients Using Simcyp Program: Applications in Clinical Practice
This prospective open-label parallel pilot clinical study evaluated the efficacy and safety of physiologically based pharmacokinetic (PBPK)-guided simvastatin dosing in Child-Pugh A and B cirrhotic patients with portal hypertension over a 3-month period. Twenty-two patients were enrolled following screening, and portal hemodynamic, laboratory, and safety parameters were assessed.
Read the detailed description
This was a prospective, open-label, parallel interventional clinical study conducted over a three-month period in Egyptian cirrhotic patients with portal hypertension.
Thirty patients were screened for eligibility. Eight patients were excluded as they did not meet the predefined inclusion criteria. A total of 22 patients were enrolled and completed the study.
Adult patients aged ≥18 years with confirmed liver cirrhosis and portal hypertension without a history of variceal bleeding were eligible for inclusion. Patients with severe renal impairment, pregnancy, known hypersensitivity to statins, active malignancy within the previous two years, or recent use of strong CYP3A4 inhibitors were excluded.
Patients were stratified according to Child-Pugh (CP) classification into CP class A and CP class B groups. Simvastatin doses were determined using physiologically based pharmacokinetic (PBPK) modeling via the Simcyp® Simulator to account for hepatic impairment-related changes in drug exposure.
CP class A patients received simvastatin 15 mg once daily, while CP class B patients received simvastatin 5 mg once daily.
Clinical evaluation included Doppler ultrasonographic assessment of portal and hepatic hemodynamics, including portal vein diameter, portal vein velocity, congestion index, and hepatic artery resistive index. Laboratory investigations included liver function tests (ALT, AST, total bilirubin, and serum albumin), renal function tests (serum creatinine and BUN), complete blood count, and creatine kinase for safety monitoring.
Patients were followed monthly throughout the 3-month study period, with systematic documentation of adverse events.
- Being tested
- Simvastatin 15 mg, Simvastatin 5 mg
- Keywords
- Liver Cirrhosis, Portal Hypertension, Simvastatin
- Medical subject headings
- Liver Cirrhosis, Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simvastatin 15 mgDrug
Simvastatin is an HMG-CoA reductase inhibitor that improves endothelial nitric oxide bioavailability and reduces intrahepatic vascular resistance, thereby potentially lowering portal pressure.
Simvastatin 5 mgDrug
Simvastatin is an HMG-CoA reductase inhibitor that improves endothelial nitric oxide bioavailability and reduces intrahepatic vascular resistance, thereby potentially lowering portal pressure.
| Study group | Role | What they receive |
|---|---|---|
| Group 1_Child-Pugh A | Experimental | 10 patients with Child-Pugh A received Simvastatin 15 mg once daily. Receives: Drug: Simvastatin 15 mg |
| Group 2_Child-Pugh B | Experimental | 12 patients with Child-Pugh B received Simvastatin 5 mg once daily. Receives: Drug: Simvastatin 5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Portal Vein Diameter (mm)
Portal vein diameter will be measured as a Doppler ultrasound parameter to evaluate changes related to portal hypertension
Measured: 3 months
Change in Portal Vein Velocity (cm/s)
Portal vein velocity will be assessed as an indicator reflecting changes in portal hypertension
Measured: 3 months
Change in Hepatic Artery Resistance Index (HARI)
The Hepatic Artery Resistance Index will be measured as a Doppler-based marker associated with changes in portal hypertension
Measured: 3 months
Change in Congestion Index (CI) (cm/ [cm/s2])
The congestion index will be evaluated as a Doppler-derived surrogate marker for portal hypertension severity
Measured: 3 months
Change in Modified Vascular Liver Index (MVLI) (cm/s)
MVLI will be measured as part of the Doppler assessment reflecting changes in portal hypertension
Measured: 3 months
Change in Platelet Count (×10⁹/L)
Platelet count will be assessed as a hematologic surrogate marker associated with portal hypertension.
Measured: 3 months
Secondary outcomes (1)
Incidence of adverse effects related to Simvastatin
Adverse effects will be monitored throughout the study period, including clinical evaluation and laboratory investigations such as liver function tests (ALT, AST), creatine kinase (CK), and documentation of any muscle-related or gastrointestinal symptoms.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2026
- Study start15 Mar 2024
- Primary completion15 Mar 2025
- Study completion15 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- More trials run by Kafrelsheikh UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kafrelsheikh University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Naira Galal, Kafrelsheikh University
- Investigators
- Naira Galal, BSc in Pharmacy, Principal investigator, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh UniversityNoha Mahmoud El-khodary, PhD, Study director, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07459972
- Sponsor's protocol ID
- KFSIRB200-127
- Status last verified
- Mar 2026
- First submitted
- 4 Mar 2026
- Last updated
- 11 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Abraldes JG, Albillos A, Banares R, Turnes J, Gonzalez R, Garcia-Pagan JC, Bosch J. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology. 2009 May;136(5):1651-8. doi: 10.1053/j.gastro.2009.01.043. Epub 2009 Jan 24.
PubMed 19208350
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Prediction for Statins and Anticoagulant Medications in Cirrhotic Patients Using Simcyp Program: Applications in Clinical Practice
- ClinicalTrials.gov ID
- NCT07459972
- Acronym / sponsor ID
- KFSIRB200-127
- Keywords
- Liver Cirrhosis, Portal Hypertension, Simvastatin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Kafrelsheikh UniversityUniversity, hospital or other
- Study start
- 15 Mar 2024 (actual)
- Primary completion
- 15 Mar 2025 (actual)
- Study completion
- 15 Jun 2025 (actual)
- First posted
- 10 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This prospective open-label parallel pilot clinical study evaluated the efficacy and safety of physiologically based pharmacokinetic (PBPK)-guided simvastatin dosing in Child-Pugh A and B cirrhotic patients with portal hypertension over a 3-month period. Twenty-two patients were enrolled following screening, and portal hemodynamic, laboratory, and safety parameters were assessed.
Detailed description
This was a prospective, open-label, parallel interventional clinical study conducted over a three-month period in Egyptian cirrhotic patients with portal hypertension.
Thirty patients were screened for eligibility. Eight patients were excluded as they did not meet the predefined inclusion criteria. A total of 22 patients were enrolled and completed the study.
Adult patients aged ≥18 years with confirmed liver cirrhosis and portal hypertension without a history of variceal bleeding were eligible for inclusion. Patients with severe renal impairment, pregnancy, known hypersensitivity to statins, active malignancy within the previous two years, or recent use of strong CYP3A4 inhibitors were excluded.
Patients were stratified according to Child-Pugh (CP) classification into CP class A and CP class B groups. Simvastatin doses were determined using physiologically based pharmacokinetic (PBPK) modeling via the Simcyp® Simulator to account for hepatic impairment-related changes in drug exposure.
CP class A patients received simvastatin 15 mg once daily, while CP class B patients received simvastatin 5 mg once daily.
Clinical evaluation included Doppler ultrasonographic assessment of portal and hepatic hemodynamics, including portal vein diameter, portal vein velocity, congestion index, and hepatic artery resistive index. Laboratory investigations included liver function tests (ALT, AST, total bilirubin, and serum albumin), renal function tests (serum creatinine and BUN), complete blood count, and creatine kinase for safety monitoring.
Patients were followed monthly throughout the 3-month study period, with systematic documentation of adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1_Child-Pugh A | Experimental | Drug: Simvastatin 15 mg10 patients with Child-Pugh A received Simvastatin 15 mg once daily. |
| Group 2_Child-Pugh B | Experimental | Drug: Simvastatin 5 mg12 patients with Child-Pugh B received Simvastatin 5 mg once daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients aged ≥ 18 years
- Confirmed diagnosis of liver cirrhosis (clinical, laboratory, or imaging evidence)
- Evidence of portal hypertension (clinical findings and/or Doppler ultrasound measurements)
- No previous history of variceal bleeding
- Child-Pugh class A or B
Key exclusion criteria (7 listed)
- Active hepatocellular carcinoma
- Severe renal impairment (eGFR < 30 mL/min/1.73 m²)
- Baseline creatine kinase (CK) > 3 × upper limit of normal
- Known hypersensitivity to simvastatin
- Current therapy with strong CYP3A4 inhibitors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Simvastatin 15 mgSimvastatin is an HMG-CoA reductase inhibitor that improves endothelial nitric oxide bioavailability and reduces intrahepatic vascular resistance, thereby potentially lowering portal pressure. | Drug | Group 1_Child-Pugh A |
| Simvastatin 5 mgSimvastatin is an HMG-CoA reductase inhibitor that improves endothelial nitric oxide bioavailability and reduces intrahepatic vascular resistance, thereby potentially lowering portal pressure. | Drug | Group 2_Child-Pugh B |
Primary outcome
Change in Portal Vein Diameter (mm)
Time frame: 3 months
Portal vein diameter will be measured as a Doppler ultrasound parameter to evaluate changes related to portal hypertension
Change in Portal Vein Velocity (cm/s)
Time frame: 3 months
Portal vein velocity will be assessed as an indicator reflecting changes in portal hypertension
Change in Hepatic Artery Resistance Index (HARI)
Time frame: 3 months
The Hepatic Artery Resistance Index will be measured as a Doppler-based marker associated with changes in portal hypertension
Change in Congestion Index (CI) (cm/ [cm/s2])
Time frame: 3 months
The congestion index will be evaluated as a Doppler-derived surrogate marker for portal hypertension severity
Change in Modified Vascular Liver Index (MVLI) (cm/s)
Time frame: 3 months
MVLI will be measured as part of the Doppler assessment reflecting changes in portal hypertension
Change in Platelet Count (×10⁹/L)
Time frame: 3 months
Platelet count will be assessed as a hematologic surrogate marker associated with portal hypertension.
1 secondary outcome
Incidence of adverse effects related to Simvastatin
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2026.
- Background: PubMed 19208350Abraldes JG, Albillos A, Banares R, Turnes J, Gonzalez R, Garcia-Pagan JC, Bosch J. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology. 2009 May;136(5):1651-8. doi: 10.1053/j.gastro.2009.01.043. Epub 2009 Jan 24.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naira Galal, BSc in Pharmacy principal investigator
Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
Noha Mahmoud El-khodary, PhD study director
Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Simvastatin 15 mg and Simvastatin 5 mg in people with Liver Cirrhosis and Portal Hypertension Related to Cirrhosis, run by Kafrelsheikh University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Portal Vein Diameter (mm) (time frame: 3 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07459972, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2026.