Efficacy and Safety of Primovist in Chinese Patients

NCT00526188 | Completed Phase 3 Results DMC

• 2 other identifiers: 91531310682
• Study Type: interventional
• Target: 234
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Known or Suspected Focal Liver Lesions

Keywords

Primovist; Chinese patients; Liver MRI

Outcome Measures

Primary Outcomes (1)

• Difference in Sensitivity of Lesion Detection in MRI Images (Post-contrast MRI Minus Pre-contrast MRI) Measured as Percentage Points

  Three Blinded Readers performed lesion detection in pre- and post-contrast MRI image sets. Per Blinded Reader/image set combination, sensitivity of lesion detection was calculated, as: (number of lesions detected in the reader/image set combination)/(number of lesions in Standard of Reference)\*100%. Then, difference in sensitivity of lesion detection for post- minus pre-contrast MRI images (in percentage points) was calculated for each Blinded Reader.

  Post administration assessment of study images (i.e. on the same day of treatment by the investigators and at the end of patient enrollment of the study from 29 September to 18 November 2008 by the Blinded Readers).

Secondary Outcomes (2)

• Difference in Sensitivity of Lesion Detection in MRI Images (Post-contrast MRI Minus Pre-contrast MRI) Assessed by Investigators Measured in Percentage Points

  Post administration assessment of study images (i.e. on the same day of treatment by the investigators and at the end of patient enrollment of the study from 29 September to 18 November 2008 by the Blinded Readers).

• Difference in Precision of Lesion Characterization (Combined Pre- and Post-contrast Minus Pre-contrast MRI) Measured in Percentage Points

  Post administration assessment of study images (i.e. on the same day of treatment by the investigators and at the end of patient enrollment of the study from 29 September to 18 November 2008 by the Blinded Readers).

Study Arms (1)

Gadoxetic Acid Disodium (Primovist, BAY86-4873)

EXPERIMENTAL

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

Drug: Gadoxetic Acid Disodium (Primovist, BAY86-4873)

Interventions

Gadoxetic Acid Disodium (Primovist, BAY86-4873) DRUG

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

Gadoxetic Acid Disodium (Primovist, BAY86-4873)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (6)

Unknown Facility

Nanjing, Jiangsu, 210009, China

Location

Unknown Facility

Suzhou, Jiangsu, 215006, China

Location

Unknown Facility

Xi'an, Shaanxi, 710032, China

Location

Unknown Facility

Beijing, 100853, China

Location

Unknown Facility

Shanghai, 200032, China

Location

Unknown Facility

Shanghai, 200433, China

Location

Related Publications (1)

• Zeng MS, Ye HY, Guo L, Peng WJ, Lu JP, Teng GJ, Huan Y, Li P, Xu JR, Liang CH, Breuer J. Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients: a multicenter, open-label, phase III study. Hepatobiliary Pancreat Dis Int. 2013 Dec;12(6):607-16. doi: 10.1016/s1499-3872(13)60096-x.

  PMID: 24322746 RESULT

MeSH Terms

Interventions

gadolinium ethoxybenzyl DTPA

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2007
• First Posted: September 10, 2007
• Study Start: August 1, 2007
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: May 1, 2015
• Results First Posted: December 30, 2009

Record last verified: 2015-04

Locations

CN (6)