Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study aims at a direct comparison between ProHance (0.1 mmol/kg) and a validated comparator Gadovist/Gadavist (0.1 mmol/kg) in a crossover intra-individual design in subjects with brain tumors to confirm the identical overall technical and diagnostic performance of the two MR contrast agents.
Adult patients were given two MRI exams, one after injection of ProHance (0.1 mmol/kg) and one after injection of Gadovist/Gadavist (0.1 mmol/kg). The exams were performed with identical equipment and imaging parameters with the order of the two exams randomized and 2-14 days between the first and the second MRI exam. Image data was evaluated by 3 expert neuroradiologist blinded to the agent administered and patient clinical data.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MRI with Gadoteridol | Active Comparator | MRI after 0.1 mmol/kg IV ProHance, then with 0.1 mmol/kg Gadovist/Gadavist. MRI performed after both agents with identical sequences. |
|
| MRI with Gadobutrol | Active Comparator | MRI after 0.1 mmol/kg IV Gadovist/Gadavist, then with 0.1 mmol/kg ProHance. MRI performed after both agents with identical sequences. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| gadoteridol | Drug | ProHance 0.1 mmol/kg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Global Diagnostic Preference Between the Two Exams | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Comparison of image sets obtained within 2 to 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Lesion Border Delineation | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Comparison of image sets obtained within 2 to 14 days |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Gianpaolo Pirovano, MD | Bracco Diagnostics, Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Holy Name Medical Center | Teaneck | New Jersey | 07666 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25300984 | Result | Maravilla KR, Smith MP, Vymazal J, Goyal M, Herman M, Baima JJ, Babbel R, Vaneckova M, Zizka J, Colosimo C, Urbanczyk-Zawadzka M, Mechl M, Bag AK, Bastianello S, Bueltmann E, Hirai T, Frattini T, Kirchin MA, Pirovano G. Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study). AJNR Am J Neuroradiol. 2015 Jan;36(1):14-23. doi: 10.3174/ajnr.A4154. Epub 2014 Oct 9. |
Not provided
Not provided
229 patients were enrolled and signed informed consent. Each enrolled patient was randomized and dosed with at least one contrast agent.
A total of 229 patients were recruited from September 2012 through November 2013 at 19 clinical trial sites. Off-site assessment of the images was performed between 21 January and 3 April 2014 by 3 board-certified neuroradiologists blinded as to which contrast agent was used, patient clinical information, and the results of other imaging studies.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 (ProHance Then Gadovist/Gadavist) | Patients randomized to receive ProHance first |
| FG001 | Sequence 2 (Gadovist/Gadavist Then ProHance) | Patients randomized to receive Gadovist/Gadavist first |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Injection |
| |||||||||||||
| Washout (no Second Injection/MRI) |
| |||||||||||||
| Second Injection |
|
Per Protocol
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | ProHance Then Gadovist/Gadavist | Per Protocol=patients who completed both exams, had global paired image data available, and had no major protocol violations |
| BG001 | Gadovist/Gadavist Then ProHance |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Global Diagnostic Preference Between the Two Exams | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Per Protocol=patients who completed both exams, had global paired image data available, and had no major protocol violations | Posted | Number | participant exams | Comparison of image sets obtained within 2 to 14 days | Patient Exams | Participants |
|
Up to 24 hours after contrast media injection
All adverse events collected were categorized using MedDRA 16.1 and tabulated
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Safety Population (ProHance) | All enrolled patients who received a randomized injection of ProHance |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
Histologic confirmation of disease available for only 139/198 patients in the PP analysis. Of these, 128 patients had confirmed brain tumors and were available for the analyses of diagnostic performance (tumor detection and tumor characterization).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gianpaolo Pirovano, MD | Executive Director, MRI | 609-514-2226 | gianpaolo.pirovano@diag.bracco.com |
Not provided
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| ID | Term |
|---|---|
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C062402 | gadoteridol |
| C090600 | gadobutrol |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| gadobutrol | Drug | Gadovist/Gadavist 0.1 mmol/kg |
|
|
| Lesion Internal Morphology | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Comparison of image sets obtained within 2 to 14 days |
| Extent of Disease | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Comparison of image sets obtained within 2 to 14 days |
| Lesion Contrast Enhancement | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Comparison of image sets obtained within 2 to 14 days |
| Lesion to Background Ratio on Post T1-weighed Spin Echo Images | Mean of difference in signal intensity postdose (ProHance - Gadovist/Gadavist) | 5-10 minutes Postdose |
| Percentage Signal Intensity Enhancement on Postdose Images | Mean difference in percentage signal intensity enhancement on postdose T1-weighted SE/FSE images (ProHance - Gadovist/Gadavist) | 5-10 minutes Postdose |
| Lesion Detection | Lesion detection rate by contrast agent and reader | 5-10 minutes Postdose |
| Accuracy for Tumor Characterization | Blinded reader assessment of accuracy of tumor characterization (benign/malignant) - patient level assessment | 5-10 minutes Postdose |
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
Per Protocol=patients who completed both exams, had global paired image data available, and had no major protocol violations
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Paired exams reviewed by Reader 2
| OG002 | Reader 3 | Paired exams reviewed by Reader 3 |
|
|
|
| Secondary | Lesion Border Delineation | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Posted | Number | participant exams | Comparison of image sets obtained within 2 to 14 days | Patient Exams | Participants |
|
|
|
|
| Secondary | Lesion Internal Morphology | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Posted | Number | participant exams | Comparison of image sets obtained within 2 to 14 days | Patient Exams | Participants |
|
|
|
|
| Secondary | Extent of Disease | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Posted | Number | participant exams | Comparison of image sets obtained within 2 to 14 days | Patient Exams | Participants |
|
|
|
|
| Secondary | Lesion Contrast Enhancement | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Posted | Number | participant exams | Comparison of image sets obtained within 2 to 14 days | Patient Exams | Participants |
|
|
|
|
| Secondary | Lesion to Background Ratio on Post T1-weighed Spin Echo Images | Mean of difference in signal intensity postdose (ProHance - Gadovist/Gadavist) | Per-protocol population | Posted | Mean | Standard Deviation | signal intensity | 5-10 minutes Postdose | Lesions | Participants |
|
|
|
|
| Secondary | Percentage Signal Intensity Enhancement on Postdose Images | Mean difference in percentage signal intensity enhancement on postdose T1-weighted SE/FSE images (ProHance - Gadovist/Gadavist) | Per-protocol population | Posted | Mean | Standard Deviation | percentage signal intensity enhancement | 5-10 minutes Postdose | Lesions | Participants |
|
|
|
|
| Secondary | Lesion Detection | Lesion detection rate by contrast agent and reader | Per protocol patients with histologically confirmed lesions | Posted | Number | participant exams | 5-10 minutes Postdose |
|
|
|
|
| Secondary | Accuracy for Tumor Characterization | Blinded reader assessment of accuracy of tumor characterization (benign/malignant) - patient level assessment | Subjects with histologically confirmed lesions | Posted | Number | participants | 5-10 minutes Postdose |
|
|
|
|
| 0 |
| 222 |
| 15 |
| 222 |
| EG001 | Safety Population (Gadovist/Gadavist) | All enrolled patients who received a randomized injection of Gadovist/Gadavist | 0 | 216 | 8 | 216 |
| Nausea | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Fatigue | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 16.1 | Systematic Assessment |
|
| Mood altered | Psychiatric disorders | MedDRA 16.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Orophanyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Vascular rupture | Vascular disorders | MedDRA 16.1 | Systematic Assessment |
|
Study results may be presented at scientific symposia or published in a peer-review journal after review by sponsor in accordance with the guidelines set forth in the applicable publication or financial agreement
|
| Gadovist/Gadavist Better |
|
P-value from Wilcoxon signed-rank test |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | 1.0 | P-value from Wilcoxon signed-rank test | 2-Sided | No | Superiority or Other |
|
| Gadovist/Gadavist betterB |
|
P-value from Wilcoxon signed-rank test |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | 1.0 | P-value from Wilcoxon signed-rank test | 2-Sided | No | Superiority or Other |
|
| Gadovist/Gadavist Better |
|
P-value from Wilcoxon signed-rank test |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | 1.0 | P-value from Wilcoxon signed-rank test | 2-Sided | No | Superiority or Other |
|
| Gadovist/Gadavist Better |
|
P-value from Wilcoxon signed-rank test |
| 2-Sided |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | 1.0 | P-value from Wilcoxon signed-rank test | 2-Sided | No | Superiority or Other |
Mixed effect model with period, sequence, and IP and fixed effect and subject nested within sequence as random effect
| 0.0676 |
| 2-Sided |
| No |
| Superiority or Other |
| Mixed Models Analysis | Mixed effect model with period, sequence, and IP and fixed effect and subject nested within sequence as random effect | 0.5267 | 2-Sided | No | Superiority or Other |
Investigation product (IP) effect from mixed model with period, sequence, and IP as fixed effects and subject nested within sequence as random effect. |
| 0.4514 |
| 2-Sided |
| No |
| Superiority or Other |
| Mixed Models Analysis | Investigation product (IP) effect from mixed model with period, sequence, and IP as fixed effects and subject nested within sequence as random effect. | 0.7722 | 2-Sided | No | Superiority or Other |
| False Negative (Pa |
|
| 2-Sided |
| No |
| Superiority or Other |
| McNemar | 0.0455 | 2-Sided | No | Superiority or Other |
| Patients with Tumors Incorrectly Categorized |
|
| McNemar |
| 0.1317 |
| 2-Sided |
| No |
| Superiority or Other |
| McNemar test of difference (ProHance minus Gadovist/Gadavist) in accuracy for tumor characterization | McNemar | 0.0124 | 2-Sided | No | Superiority or Other |