Efficacy and Safety of Primovist in Chinese Patients
Condition: Known or Suspected Focal Liver Lesions
Intervention: Gadoxetic Acid Disodium (Primovist, BAY86-4873)
Intervention description: Bolus injection of 0.025 mmol/kg body weight (0.1 ml/kg BW) of Gadoxetic Acid Disodium (Primovist, BAY86-4873). Single i.v. injection during MRI procedure, with one contrast-enhanced MRI procedure per patient
Phase: Phase 3
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 234.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Primovist; Chinese patients; Liver MRI

Summary:

      Participants who had been diagnosed or suspected by doctors to have focal liver lesions that
      need further evaluation in order to make an accurate diagnosis. Participants would need to
      have an enhanced magnetic resonance imaging (MRI) scan so that doctors could have further
      information about the number and characteristics of the focal liver lesions.

      Participants were invited to take part in this clinical study. The purpose of this study was
      to evaluate Primovist, which is a liver-specific MRI contrast medium, on the efficacy of
      lesion detection and characterization, and tolerability in Chinese patients with known or
      suspected focal liver lesions.

      Primovist, the investigational drug in this study, is a liver-specific MRI contrast medium
      developed by Bayer Schering Pharma AG. Its active substance is Gd-EOB-DTPA. Primovist was
      first approved in 2004 in Sweden followed by an approval in the European community, in
      Switzerland and Australia in the same year.

      Procedures:

      Before entry into the study and after entry of the study a physical examination was
      conducted, blood pressure and heart rate were measured, blood and urine samples were taken.
      Current medications and medical conditions (including suspected pregnancy) and medical and
      surgical history were elicited by doctors.

      After entry into the study, participants were scheduled to have an MRI examination, which
      lasted about 25-35 minutes.

      During the MRI examination, an initial MRI scan without contrast was acquired which followed
      by another MRI series after the intravenous administration of Primovist.

      The following day participants were asked to return to the hospital for a follow-up safety
      evaluation.

      Possible Benefit Participants were scheduled to receive an enhanced magnetic resonance
      imaging scan. Clinical studies indicated that Primovist increased the efficacy of detection
      and characterization of focal liver lesions by providing better contrast between the focal
      liver lesions and surrounding normal tissue. Primovist were shown to provide additional
      information regarding existence, number and characterization (lesion or non-lesion, malignant
      or benign) of these abnormalities.

      Based on the experience with patients given Primovist, some adverse reactions were observed.

      Most of undesirable effects were transient and of mild to moderate intensity. The most
      commonly noted adverse events (AEs) in subjects receiving Primovist for MRI were nausea and
      headache with an incidence of 1.1%. Other AEs that occurred in 0.5% of the subject population
      were feeling hot (0.8%), back pain (0.6%) and dizziness (0.5%).

      All other AEs occurred in less than 0.5% of the patients, e.g. anxiety; coughing; eye
      disorder; fever; flatulence; generalized spasm; hypertension; injection site symptoms
      including edema, inflammation, and reaction; lightheadedness; parosmia; postural hypotension;
      taste perversion, motoric unrest; acute respiratory distress; fatigue; malaise; vomiting;
      palpitations, erythema, chest pain and back pain.

      Coldness, warmth or pain at the injection site, injection site reaction, and injection site
      accumulation of fluid were rare. In very rare cases strong allergy-like reactions ranging to
      shock may occur.

      Post-marketing tachycardia and restlessness have been reported. As in the case of other
      investigational drugs, there may also be unforeseen side effects.

      Additional information concerning all Gadolinium- based contrast agents Primovist contains
      the rare earth metal gadolinium as active ingredient. There have been reports of nephrogenic
      systemic fibrosis (NSF) associated with use of some gadolinium-containing contrast agents
      (especially Omniscan) in patients with severe renal impairment. NSF is a systemic disease
      characterised by formation of connective tissue in the skin, which becomes thickened and
      hard, sometimes leading to contractures and joint immobility. The clinical course is usually
      progressive and currently no treatment is available. To date NSF has only been reported in
      association with some Gd-containing contrast agents, but the role of these contrast agents in
      the overall pathogenesis of the disease is still not completely understood.

      No reports of patients with NSF after administration of Primovist® are known. The risk to
      trigger NSF in risk patients with severe renal impairment is considered to be low for
      Primovist® due to the low dose given and the additional excretion via feces. Furthermore the
      participation of patients with severe renal impairment are excluded from this study.

      In case the participants were suffering from renal insufficiency, they were told to tell
      their doctors prior to application of the contrast agent. In case the participants
      experienced any new alterations of the skin following the administration of the contrast
      agent, they were told to contact their doctors as soon as possible after they had recognized
      these symptoms.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients between 18 and 75 years of age inclusive.

          -  Patients (men or women) with at least one focal liver lesion, either identified or
             suspected by ultrasound (US), Computed Tomography (CT)/spiral-CT, conventional
             angiography, CT-angiography (CTA), CT-arterioportography (CTAP) or unenhanced /
             contrast-enhanced MRI* within 2 months before entering the study

        For reference, the following pathologies will meet the definition of 'focal liver lesions':

          -  Hepatocellular carcinoma

          -  Cholangiole carcinoma

          -  Metastasis

          -  Focal lymphoma

          -  Adenoma

          -  Focal nodular hyperplasia

          -  Hemangioma

          -  Abscess

          -  Focal liver fibrosis

          -  Regenerative nodules

          -  Focal fatty infiltration

          -  Hydatid cyst

          -  Liver cyst

          -  Focal sparing in fatty liver

          -  Others

          -  Patients willing to undergo study procedures including safety follow-up

          -  Patients who have undergone or who are scheduled to undergo the defined procedure for
             SOR within one month before or after the study MRI

          -  Women of child-bearing potential with negative urine pregnancy test result within 24
             hours before contrast medium (CM) injection

          -  Patients who are fully informed about the study and have signed the informed consent
             form

        Exclusion Criteria:

          -  Patients who have previously entered this study

          -  Patients who have received any contrast material within 24 hours before injection with
             study drug, or who are scheduled to receive any contrast material within 24 hours
             after injection

          -  Patients who are, or suspected to be, nursing

          -  Patients who require emergency treatment

          -  Patients with severely impaired hepatic or renal functions (e.g. serum
             glutamic-pyruvic transaminase (SGPT) twice the upper limit of reference range, acute
             renal failure)

          -  Patients who are clinically unstable and whose clinical course during the observation
             period is unpredictable (e.g. due to previous surgery, acute myocardial infarction)

          -  Patients with any physical or mental status that interferes with the signing of
             informed consent

          -  Patients with known anaphylactoid or anaphylactic reaction to any contrast media or
             hypersensitivity to any allergen including drugs

          -  Patients with a contraindication for MRI

          -  Patients who are scheduled for liver biopsy/surgery or other surgeries within 24 hours
             after injection with contrast media, or who would have a biopsy within 24 hours before
             planned injection with contrast media

          -  Patients who are likely to have any therapy or change in therapy between the study MRI
             and the procedures for the SOR