Download PDF

Clinical Trial Results:
Safety and tolerability of the combination of simvastatin plus rifaximin in patients with decompensated cirrhosis: a multicenter, double-blind, placebo controlled randomized clinical trial.

Summary
EudraCT number	2016-004499-23
Trial protocol	ES NL GB FR
Global end of trial date	12 Mar 2018

Results information
Results version number	v1(current)
This version publication date	22 Jul 2020
First version publication date	22 Jul 2020
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

LIVERHOPE_SAFETY

ISRCTN number

US NCT number

NCT03150459

WHO universal trial number (UTN)

Sponsor organisation name

IDIBAPS

Sponsor organisation address

Rosselló, 149, Barcelona, Spain, 08036

Public contact

Pere Ginés, Hospital Clínic, +34 9322754001713, pgines@clinic.cat

Scientific contact

Pere Ginés, Hospital Clínic, +34 9322754001713, pgines@clinic.cat

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

02 Aug 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

12 Mar 2018

Global end of trial reached?

Yes

Global end of trial date

12 Mar 2018

Was the trial ended prematurely?

Main objective of the trial

To evaluate the treatment-related toxicity of oral administration of simvastatin plus rifaximin in patients with decompensated cirrhosis.

Protection of trial subjects

Not required

Background therapy

Evidence for comparator

Actual start date of recruitment

26 Jul 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 5

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

Spain: 11

Country: Number of subjects enrolled

Netherlands: 3

Country: Number of subjects enrolled

France: 5

Country: Number of subjects enrolled

Italy: 16

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Trial subjects were recruited at 9 European European University Hospitals in Spain, Germany, UK, The Netherlands, Italy and France. Recruitment period: 28-July-2017 to 2-January-2018

Screening details

Having given consent, participants will undergo screening assessments to verify their eligibility to participate in the study according the selection criteria specified in the protocol. Study population was adult patients with decompensated cirrhosis.

Period 1 title

Baseline

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer

Blinding implementation details

It is a double-blind placebo controlled clinical trial

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo of simvastatin + Placebo of rifaximin

Arm type

Placebo

Investigational medicinal product name

Placebo of simvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

2 tablets every 24 hours at night during 12 weeks

Investigational medicinal product name

Placebo of rifaximin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

One tablet of Placebo of Rifaximin every 8 hours during 12 weeks

Simvastatin 20 mg

Arm description

Simvastatin 20mg/day + Rifaximin 400mg/8 hours

Arm type

Experimental

Investigational medicinal product name

Simvastatin 20 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

1 tablet of simvastatin 20 mg every 24 hours at night during 12 weeks

Investigational medicinal product name

Placebo of simvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

2 tablets every 24 hours at night during 12 weeks

Investigational medicinal product name

Rifaximin 400 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

One tablet of Rifaximin 400 mg every 8 hours during 12 weeks

Simvastatin 40 mg

Arm description

Simvastatin 40 mg + Rifaximin 400 mg

Arm type

Experimental

Investigational medicinal product name

Simvastatin 20 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

1 tablet of simvastatin 20 mg every 24 hours at night during 12 weeks

Investigational medicinal product name

Rifaximin 400 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

1 tablet of Rifaximin 400 mf every 8 hours during 12 weeks

Number of subjects in period 1	Placebo	Simvastatin 20 mg	Simvastatin 40 mg
Started	14	14	16
Completed	14	14	16

Period 2 title

Overall trial

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer

Blinding implementation details

It is a double-blind placebo controlled clinical trial

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo of simvastatin + Placebo of rifaximin

Arm type

Placebo

Investigational medicinal product name

Placebo of simvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

2 tablets every 24 hours at night during 12 weeks

Investigational medicinal product name

Placebo of rifaximin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

One tablet of Placebo of Rifaximin every 8 hours during 12 weeks

Simvastatin 20 mg

Arm description

Simvastatin 20mg/day + Rifaximin 400mg/8 hours

Arm type

Experimental

Investigational medicinal product name

Simvastatin 20 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

1 tablet of simvastatin 20 mg every 24 hours at night during 12 weeks

Investigational medicinal product name

Placebo of simvastatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

2 tablets every 24 hours at night during 12 weeks

Investigational medicinal product name

Rifaximin 400 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

One tablet of Rifaximin 400 mg every 8 hours during 12 weeks

Simvastatin 40 mg

Arm description

Simvastatin 40 mg + Rifaximin 400 mg

Arm type

Experimental

Investigational medicinal product name

Simvastatin 20 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

1 tablet of simvastatin 20 mg every 24 hours at night during 12 weeks

Investigational medicinal product name

Rifaximin 400 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

1 tablet of Rifaximin 400 mf every 8 hours during 12 weeks

Number of subjects in period 2	Placebo	Simvastatin 20 mg	Simvastatin 40 mg
Started	14	14	16
Completed	12	12	5
Not completed	2	2	11
Consent withdrawn by subject	1	1	5
Adverse event, non-fatal	1	-	5
Liver transplantation	-	1	-
Prematurely discontinuation (DSMB recommendation)	-	-	1

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Placebo of simvastatin + Placebo of rifaximin

Reporting group title

Simvastatin 20 mg

Reporting group description

Simvastatin 20mg/day + Rifaximin 400mg/8 hours

Reporting group title

Simvastatin 40 mg

Reporting group description

Simvastatin 40 mg + Rifaximin 400 mg

Reporting group values	Placebo	Simvastatin 20 mg	Simvastatin 40 mg	Total
Number of subjects	14	14	16	44
Age categorical
median age 18-64
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	10	14	11	35
From 65-84 years	4	0	5	9
85 years and over	0	0	0	0
Age continuous
55.89 (11.58)
Units: years
median (standard deviation)	59 ± 12	49 ± 11	60 ± 12	-
Gender categorical
Units: Subjects
Female	5	3	4	12
Male	9	11	12	32
Etiology of cirrhosis
Units: Subjects
Alcohol	9	9	9	27
Others	5	5	7	17
CHild Pugh class
Units: Subjects
Child B	10	10	12	32
CHild C	4	4	4	12
MELD score
Units: no
arithmetic mean (standard deviation)	13 ± 3	14 ± 3	14 ± 3	-

End points

Top of page

Reporting group title

Placebo

Reporting group description

Placebo of simvastatin + Placebo of rifaximin

Reporting group title

Simvastatin 20 mg

Reporting group description

Simvastatin 20mg/day + Rifaximin 400mg/8 hours

Reporting group title

Simvastatin 40 mg

Reporting group description

Simvastatin 40 mg + Rifaximin 400 mg

Reporting group title

Placebo

Reporting group description

Placebo of simvastatin + Placebo of rifaximin

Reporting group title

Simvastatin 20 mg

Reporting group description

Simvastatin 20mg/day + Rifaximin 400mg/8 hours

Reporting group title

Simvastatin 40 mg

Reporting group description

Simvastatin 40 mg + Rifaximin 400 mg

Primary: Liver toxicity

Top of page

End point title

Liver toxicity

End point description

(1) liver toxicity assessed by the development of liver injury defined as 3-fold increase in serum transaminases to a final value at least 3 times the upper normal limit, or 2-fold increase in serum levels of alkaline phosphatase with respect to baseline value to a final value at least 2 times the upper normal limit

End point type

Primary

End point timeframe

12 weeks of treatment period

End point values	Placebo	Simvastatin 20 mg	Simvastatin 40 mg
Number of subjects analysed	14	14	16
Units: IU/L	14	14	16

primary endpoint liver toxicity

Comparison groups

Simvastatin 20 mg v Placebo v Simvastatin 40 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.05

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

90%

sides

2-sided

lower limit

upper limit

Primary: Muscle toxicity

Top of page

End point title

Muscle toxicity

End point description

2) muscle toxicity, defined as 5-fold increase in creatinine kinase (CK) levels during treatment.

End point type

Primary

End point timeframe

12 weeks treatment period

End point values	Placebo	Simvastatin 20 mg	Simvastatin 40 mg
Number of subjects analysed	14	14	16
Units: IU/l	14	14	16

primary endpoint muscle toxicity

Comparison groups

Placebo v Simvastatin 20 mg v Simvastatin 40 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.05

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

90%

sides

2-sided

lower limit

upper limit

Adverse events

Top of page

Timeframe for reporting adverse events

12 weeks

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Placebo

Reporting group description

Reporting group title

Simvastatina 20

Reporting group description

Reporting group title

Simnvastatina 40

Reporting group description

Serious adverse events	Placebo	Simvastatina 20	Simnvastatina 40
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 14 (28.57%)	3 / 14 (21.43%)	9 / 16 (56.25%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Hepatitis toxic
subjects affected / exposed	4 / 14 (28.57%)	3 / 14 (21.43%)	9 / 16 (56.25%)
occurrences causally related to treatment / all	1 / 6	0 / 3	4 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Encephalopathy
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic encephalopathy
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Peritonitis bacterial
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatic encephalopathy
subjects affected / exposed	2 / 14 (14.29%)	1 / 14 (7.14%)	1 / 16 (6.25%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	1 / 16 (6.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Fistula
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Muscle spasms
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myopathy
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	2 / 16 (12.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Placebo	Simvastatina 20	Simnvastatina 40
Total subjects affected by non serious adverse events
subjects affected / exposed	11 / 14 (78.57%)	10 / 14 (71.43%)	15 / 16 (93.75%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	1 / 16 (6.25%)
occurrences all number	0	2	1
Chest pain
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	0	1	0
Fatigue
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	0	1	0
Influenza like illness
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	2
Malaise
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	1 / 16 (6.25%)
occurrences all number	0	1	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	1	1	0
Dyspnoea
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	0	1	0
Epistaxis
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	0	1	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences all number	1	0	0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 14 (7.14%)	2 / 14 (14.29%)	0 / 16 (0.00%)
occurrences all number	1	2	0
Weight increased
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Paracentesis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences all number	2	0	0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Hepatitis toxic
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Nervous system disorders
Amnesia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences all number	1	0	0
Encephalopathy
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Headache
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	0	1	0
Hepatic encephalopathy
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences all number	2	0	0
Iron deficiency anaemia
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	0	1	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences all number	1	0	0
Eye disorders
Conjunctivitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences all number	1	0	0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Abdominal pain
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	0	1	0
Abdominal pain upper
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Ascites
subjects affected / exposed	2 / 14 (14.29%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	3	3	0
Constipation
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Diarrhoea
subjects affected / exposed	1 / 14 (7.14%)	2 / 14 (14.29%)	3 / 16 (18.75%)
occurrences all number	1	2	3
Dyspepsia
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	0	1	0
Rectal haemorrhage
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Vomiting
subjects affected / exposed	0 / 14 (0.00%)	2 / 14 (14.29%)	0 / 16 (0.00%)
occurrences all number	0	2	0
Peritonitis bacterial
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Hepatobiliary disorders
Ascites
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	3
Hepatic encephalopathy
subjects affected / exposed	2 / 14 (14.29%)	1 / 14 (7.14%)	1 / 16 (6.25%)
occurrences all number	4	1	1
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences all number	1	0	0
Pruritus
subjects affected / exposed	4 / 14 (28.57%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	4	1	0
Renal and urinary disorders
Polyuria
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Acute kidney injury
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	2 / 16 (12.50%)
occurrences all number	1	1	2
Musculoskeletal and connective tissue disorders
Fistula
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences all number	1	0	0
Muscle spasms
subjects affected / exposed	2 / 14 (14.29%)	1 / 14 (7.14%)	1 / 16 (6.25%)
occurrences all number	3	1	1
Myalgia
subjects affected / exposed	0 / 14 (0.00%)	3 / 14 (21.43%)	2 / 16 (12.50%)
occurrences all number	0	3	2
Myopathy
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Myositis
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Rhabdomyolysis
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	2 / 16 (12.50%)
occurrences all number	0	0	2
Infections and infestations
Furuncle
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 16 (0.00%)
occurrences all number	1	0	0
Pneumonia
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	0	1	0
Upper respiratory tract infection
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Urinary tract infection
subjects affected / exposed	3 / 14 (21.43%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	4	0	1
Escherichia urinary tract infection
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Enterocolitis infectious
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	0	1	0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	1
Hyponatraemia
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	0 / 16 (0.00%)
occurrences all number	1	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

20 Mar 2017

The objective of the amendment is the correction of some errors detected related to the amount of blood and urine required during the follow-up of the study and their timepoints.

23 Oct 2017

The aim of the substantial amendment was the introduction of the following modifications: 1. Addition of the definition of women of child-bearing potential. 2. Addition of a urine pregnancy test at baseline. 3. Addition of a telephone contact visit 4 weeks after study completion. 4. Addition of cyclosporine and simeprevir as nonpermitted medication. 5. Correction of the group to which clarithromycin and telithromycin belong. 6. Removal week 2 visit as a timepoint for secondary endpoints 2, 3, 4 and 5 and as a timepoint for collecting samples for storage at the biobank. 7. Replacement of the principal investigator in Bologna University Hospital.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
12 Mar 2018	On 13th February 2018, the DSMB concluded during its regular meeting to recommend stopping one of the arms of the LIVERHOPE SAFETY study because of safety concerns. The decision to stop one of the arms of the trial was made because the data indicated that there was a higher prevalence of early study discontinuation (either because of adverse events or patient decision) in this group as compared with the other two groups. After extensive discussion within the executive committee of the LIVERHOPE SAFETY study and the Principal Investigators from the partner centers involved, the 16th February 2018 it was agreed unanimously to support this recommendation. This implied to stop therapy in those patients that were still active, but only in this specific treatment arm. In the other two arms, there were no safety concerns during the trial until that moment. Patients remaining active in the other two arms continued in the study until the end of the 12 week treatment period, the end of study according to the protocol. Only one patient was on treatment with the affected study arm and discontinued the study treatment the 16th February 2018. The blindness was maintained. The affected treatment arm has been identified at the time of the analysis of the results. The study arm concerned was Simvastatin 40mg + Rifaximin 400mg.	-

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/31607677

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
Safety and tolerability of the combination of simvastatin plus rifaximin in patients with decompensated cirrhosis: a multicenter, double-blind, placebo controlled randomized clinical trial.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Liver toxicity

Primary: Liver toxicity

Primary: Muscle toxicity

Primary: Muscle toxicity

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Safety and tolerability of the combination of simvastatin plus rifaximin in patients with decompensated cirrhosis: a multicenter, double-blind, placebo controlled randomized clinical trial.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Liver toxicity

Primary: Liver toxicity

Primary: Muscle toxicity

Primary: Muscle toxicity

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
Safety and tolerability of the combination of simvastatin plus rifaximin in patients with decompensated cirrhosis: a multicenter, double-blind, placebo controlled randomized clinical trial.