Trial Outcomes & Findings for Simvastatin in Preventing Liver Cancer in Patients With Liver Cirrhosis (NCT NCT02968810)
NCT ID: NCT02968810
Last Updated: 2025-09-17
Results Overview
Assessed by liquid-phase binding assay. Mean AFP-L3% difference calculated including all participants imputing undetectable values with 0.5%
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE2
Target enrollment
52 participants
Primary outcome timeframe
Baseline to 6 months
Results posted on
2025-09-17
Participant Flow
59 participants were randomized. 52 out of 59 participants started study agent.
Participant milestones
| Measure |
Group I (Simvastatin)
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Study
STARTED
|
28
|
24
|
|
Overall Study
COMPLETED
|
25
|
20
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
| Measure |
Group I (Simvastatin)
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
3
|
|
Overall Study
Disease Progression
|
0
|
1
|
Baseline Characteristics
Simvastatin in Preventing Liver Cancer in Patients With Liver Cirrhosis
Baseline characteristics by cohort
| Measure |
Group I (Simvastatin)
n=28 Participants
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
n=24 Participants
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58 years
STANDARD_DEVIATION 9.0 • n=93 Participants
|
59 years
STANDARD_DEVIATION 7.4 • n=4 Participants
|
59 years
STANDARD_DEVIATION 8.3 • n=27 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
30 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
12 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
25 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=93 Participants
|
19 Participants
n=4 Participants
|
43 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
Puerto Rico
|
4 participants
n=93 Participants
|
3 participants
n=4 Participants
|
7 participants
n=27 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=93 Participants
|
21 participants
n=4 Participants
|
45 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline to 6 monthsAssessed by liquid-phase binding assay. Mean AFP-L3% difference calculated including all participants imputing undetectable values with 0.5%
Outcome measures
| Measure |
Group I (Simvastatin)
n=25 Participants
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
n=20 Participants
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Change in Serum AFP-L3%
|
0.24 percent
Standard Deviation 1.00
|
-0.04 percent
Standard Deviation 0.11
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsAssessed by liquid-phase binding assay. Mean difference in AFP, a glycoform produced by malignant liver cells.
Outcome measures
| Measure |
Group I (Simvastatin)
n=25 Participants
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
n=20 Participants
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Change in Serum AFP
|
.39 ng/ml
Standard Deviation 1.33
|
-0.09 ng/ml
Standard Deviation 0.4
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsMean difference in IL-6 (interleukin-6) NPX (normalized protein expression).
Outcome measures
| Measure |
Group I (Simvastatin)
n=25 Participants
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
n=20 Participants
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Change in Serum IL-6
|
-0.49 normalized protein expression
Interval -1.39 to 0.15
|
0.25 normalized protein expression
Interval -0.31 to 0.48
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsAssessed by liquid chromatography coupled with mass spectrometry. Median difference in serum DCA (deoxycholic acid), a secondary bile acid.
Outcome measures
| Measure |
Group I (Simvastatin)
n=25 Participants
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
n=20 Participants
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Change in Serum Deoxycholic Acid
|
0.00 pmol/gram
Interval -60.0 to 55.3
|
0.00 pmol/gram
Interval -68.0 to 4.89
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsAssessed by liver elastography. Fibroscan score from a fibroscan examination (a non-invasive measurement of liver fibrosis). A test result of greater than 20kPa is generally associated with an increased HCC risk. Mean difference in liver stiffness.
Outcome measures
| Measure |
Group I (Simvastatin)
n=25 Participants
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
n=20 Participants
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Change in Liver Stiffness
|
3.89 kPA
Standard Deviation 15
|
3.83 kPA
Standard Deviation 14.1
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsThe Fib-4 index is a non-invasive measure of liver stiffness. A high score (FIB4 ≥ 3.25) and low score is (FIB4 \< 1.3) The FIB-4 index is calculated as follows: FIB-4 = (Age × AST (U/L)) ÷ (PLT (109/L) × (√ ALT (U/L)). Change in mean difference.
Outcome measures
| Measure |
Group I (Simvastatin)
n=25 Participants
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
n=20 Participants
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Change in Fibrosis 4 Index Score
|
0.4 score on a scale
Standard Deviation 1.20
|
0.17 score on a scale
Standard Deviation 1.22
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsThe Model for End-Stage Liver Disease (MELD) is a validated predictor of survival among different populations of patients with advanced liver disease. MELD = 9.57 x ln(creatinine \[mg/dL\]) + 3.78 x ln(total bilirubin \[mg/dL\]) + 11.2 x ln(INR) + 6.43. Scores range from 6 (low/ less liver disease) to 40 (high/severe liver disease). Change in mean difference.
Outcome measures
| Measure |
Group I (Simvastatin)
n=25 Participants
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
n=20 Participants
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Change in Model for End-Stage Liver Disease Score
|
0.57 score on a scale
Standard Deviation 2.76
|
0.18 score on a scale
Standard Deviation 1.61
|
Adverse Events
Group I (Simvastatin)
Serious events: 3 serious events
Other events: 24 other events
Deaths: 0 deaths
Group II (Placebo)
Serious events: 3 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group I (Simvastatin)
n=28 participants at risk
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
n=24 participants at risk
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
4.2%
1/24 • Number of events 1 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
4.2%
1/24 • Number of events 1 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Infections and infestations
Infections and infestations - Other, specify
|
3.6%
1/28 • Number of events 1 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Gastrointestinal disorders
Ascites
|
3.6%
1/28 • Number of events 1 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, specify
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
4.2%
1/24 • Number of events 1 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
|
3.6%
1/28 • Number of events 1 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
Other adverse events
| Measure |
Group I (Simvastatin)
n=28 participants at risk
Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
Group II (Placebo)
n=24 participants at risk
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
7.1%
2/28 • Number of events 3 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Gastrointestinal disorders
Nausea
|
14.3%
4/28 • Number of events 5 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
8.3%
2/24 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
8.3%
2/24 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
12.5%
3/24 • Number of events 3 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Gastrointestinal disorders
Dyspepsia
|
7.1%
2/28 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
10.7%
3/28 • Number of events 3 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify (inguinal hernia)
|
7.1%
2/28 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
General disorders
Fatigue
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
25.0%
6/24 • Number of events 6 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
General disorders
Flu like symptoms
|
14.3%
4/28 • Number of events 4 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
16.7%
4/24 • Number of events 4 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
8.3%
2/24 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Investigations
Aspartate aminotransferase increased
|
10.7%
3/28 • Number of events 3 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Investigations
Blood bilirubin increased
|
7.1%
2/28 • Number of events 4 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
8.3%
2/24 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Investigations
Platelet count decreased
|
7.1%
2/28 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
8.3%
2/24 • Number of events 3 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.1%
2/28 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
12.5%
3/24 • Number of events 3 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
2/28 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.1%
2/28 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
16.7%
4/24 • Number of events 4 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
16.7%
4/24 • Number of events 4 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Nervous system disorders
Headache
|
21.4%
6/28 • Number of events 16 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
25.0%
6/24 • Number of events 12 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Psychiatric disorders
Anxiety
|
7.1%
2/28 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Psychiatric disorders
Insomnia
|
7.1%
2/28 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.1%
2/28 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
12.5%
3/24 • Number of events 3 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
8.3%
2/24 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
8.3%
2/24 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
8.3%
2/24 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
7.1%
2/28 • Number of events 2 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
0.00%
0/24 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
|
Vascular disorders
Hypertension
|
0.00%
0/28 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
8.3%
2/24 • Number of events 3 • Collected from the time informed consent was signed and baseline procedures were completed through 90 days post-intervention.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60