Trial Outcomes & Findings for Comparison of Prohance® With Gadovist®/Gadavist™ in Magnetic Resonance Imaging (MRI) of the Brain (NCT NCT01613417)

NCT ID: NCT01613417

Last Updated: 2015-07-01

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 229 participants
• Primary outcome timeframe: Comparison of image sets obtained within 2 to 14 days
• Results posted on: 2015-07-01

Participant Flow

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.

229 patients were enrolled and signed informed consent. Each enrolled patient was randomized and dosed with at least one contrast agent.

Participant milestones

Measure	Sequence 1 (ProHance Then Gadovist/Gadavist) Patients randomized to receive ProHance first	Sequence 2 (Gadovist/Gadavist Then ProHance) Patients randomized to receive Gadovist/Gadavist first
First Injection STARTED	113	116
First Injection COMPLETED	113	116
First Injection NOT COMPLETED	0	0
Washout (no Second Injection/MRI) STARTED	113	116
Washout (no Second Injection/MRI) COMPLETED	100	109
Washout (no Second Injection/MRI) NOT COMPLETED	13	7
Second Injection STARTED	100	109
Second Injection COMPLETED	100	109
Second Injection NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Sequence 1 (ProHance Then Gadovist/Gadavist) Patients randomized to receive ProHance first	Sequence 2 (Gadovist/Gadavist Then ProHance) Patients randomized to receive Gadovist/Gadavist first
Washout (no Second Injection/MRI) Withdrawal by Subject	13	7

Baseline Characteristics

Comparison of Prohance® With Gadovist®/Gadavist™ in Magnetic Resonance Imaging (MRI) of the Brain

Baseline characteristics by cohort

Measure	ProHance Then Gadovist/Gadavist n=93 Participants Per Protocol=patients who completed both exams, had global paired image data available, and had no major protocol violations	Gadovist/Gadavist Then ProHance n=105 Participants Per Protocol=patients who completed both exams, had global paired image data available, and had no major protocol violations	Total n=198 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	70 Participants n=5 Participants	70 Participants n=7 Participants	140 Participants n=5 Participants
Age, Categorical >=65 years	23 Participants n=5 Participants	35 Participants n=7 Participants	58 Participants n=5 Participants
Age, Continuous	54.5 years STANDARD_DEVIATION 14.27 • n=5 Participants	55.9 years STANDARD_DEVIATION 14.29 • n=7 Participants	55.2 years STANDARD_DEVIATION 14.31 • n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	58 Participants n=7 Participants	108 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	47 Participants n=7 Participants	90 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	88 Participants n=5 Participants	102 Participants n=7 Participants	190 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	46 participants n=5 Participants	46 participants n=7 Participants	92 participants n=5 Participants
Region of Enrollment Europe	39 participants n=5 Participants	51 participants n=7 Participants	90 participants n=5 Participants
Region of Enrollment Canada	8 participants n=5 Participants	8 participants n=7 Participants	16 participants n=5 Participants

PRIMARY outcome

Timeframe: Comparison of image sets obtained within 2 to 14 days

Population: Per Protocol=patients who completed both exams, had global paired image data available, and had no major protocol violations

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.

Outcome measures

Measure	Reader 1 n=198 Patient Exams Paired exams reviewed by Reader 1	Reader 2 n=194 Patient Exams Paired exams reviewed by Reader 2	Reader 3 n=196 Patient Exams Paired exams reviewed by Reader 3	Reader 2 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg	Reader 3 - ProHance MRI after ProHance 0.1 mmol/kg	Reader 3 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg
Global Diagnostic Preference Between the Two Exams ProHance Preferred	14 participant exams	7 participant exams	1 participant exams	—	—	—
Global Diagnostic Preference Between the Two Exams Contrast Agents Equal	171 participant exams	180 participant exams	195 participant exams	—	—	—
Global Diagnostic Preference Between the Two Exams Gadovist/Gadavist Preferred	13 participant exams	7 participant exams	0 participant exams	—	—	—

SECONDARY outcome

Timeframe: Comparison of image sets obtained within 2 to 14 days

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.

Outcome measures

Measure	Reader 1 n=198 Patient Exams Paired exams reviewed by Reader 1	Reader 2 n=194 Patient Exams Paired exams reviewed by Reader 2	Reader 3 n=196 Patient Exams Paired exams reviewed by Reader 3	Reader 2 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg	Reader 3 - ProHance MRI after ProHance 0.1 mmol/kg	Reader 3 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg
Lesion Border Delineation ProHance Better	8 participant exams	2 participant exams	1 participant exams	—	—	—
Lesion Border Delineation No Difference between Prohance and Gadovist/Gadavi	181 participant exams	189 participant exams	195 participant exams	—	—	—
Lesion Border Delineation Gadovist/Gadavist Better	9 participant exams	3 participant exams	0 participant exams	—	—	—

SECONDARY outcome

Timeframe: Comparison of image sets obtained within 2 to 14 days

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.

Outcome measures

Measure	Reader 1 n=198 Patient Exams Paired exams reviewed by Reader 1	Reader 2 n=194 Patient Exams Paired exams reviewed by Reader 2	Reader 3 n=196 Patient Exams Paired exams reviewed by Reader 3	Reader 2 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg	Reader 3 - ProHance MRI after ProHance 0.1 mmol/kg	Reader 3 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg
Lesion Internal Morphology ProHance better	2 participant exams	2 participant exams	1 participant exams	—	—	—
Lesion Internal Morphology No Difference Between ProHance and Gadovist/Gadavi	195 participant exams	188 participant exams	195 participant exams	—	—	—
Lesion Internal Morphology Gadovist/Gadavist betterB	1 participant exams	4 participant exams	0 participant exams	—	—	—

SECONDARY outcome

Timeframe: Comparison of image sets obtained within 2 to 14 days

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.

Outcome measures

Measure	Reader 1 n=198 Patient Exams Paired exams reviewed by Reader 1	Reader 2 n=194 Patient Exams Paired exams reviewed by Reader 2	Reader 3 n=196 Patient Exams Paired exams reviewed by Reader 3	Reader 2 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg	Reader 3 - ProHance MRI after ProHance 0.1 mmol/kg	Reader 3 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg
Extent of Disease ProHance Better	1 participant exams	2 participant exams	1 participant exams	—	—	—
Extent of Disease No Difference between ProHance and Gadovist/Gadavi	196 participant exams	190 participant exams	195 participant exams	—	—	—
Extent of Disease Gadovist/Gadavist Better	1 participant exams	2 participant exams	0 participant exams	—	—	—

SECONDARY outcome

Timeframe: Comparison of image sets obtained within 2 to 14 days

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.

Outcome measures

Measure	Reader 1 n=198 Patient Exams Paired exams reviewed by Reader 1	Reader 2 n=194 Patient Exams Paired exams reviewed by Reader 2	Reader 3 n=196 Patient Exams Paired exams reviewed by Reader 3	Reader 2 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg	Reader 3 - ProHance MRI after ProHance 0.1 mmol/kg	Reader 3 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg
Lesion Contrast Enhancement ProHance Better	14 participant exams	10 participant exams	2 participant exams	—	—	—
Lesion Contrast Enhancement No Difference between ProHance and Gadovist/Gadavi	170 participant exams	174 participant exams	193 participant exams	—	—	—
Lesion Contrast Enhancement Gadovist/Gadavist Better	14 participant exams	10 participant exams	1 participant exams	—	—	—

SECONDARY outcome

Timeframe: 5-10 minutes Postdose

Population: Per-protocol population

Mean of difference in signal intensity postdose (ProHance - Gadovist/Gadavist)

Outcome measures

Measure	Reader 1 n=194 Lesions Paired exams reviewed by Reader 1	Reader 2 n=137 Lesions Paired exams reviewed by Reader 2	Reader 3 n=162 Lesions Paired exams reviewed by Reader 3	Reader 2 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg	Reader 3 - ProHance MRI after ProHance 0.1 mmol/kg	Reader 3 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg
Lesion to Background Ratio on Post T1-weighed Spin Echo Images	-0.02 signal intensity Standard Deviation 0.17	-0.16 signal intensity Standard Deviation 1.12	-0.01 signal intensity Standard Deviation 0.18	—	—	—

SECONDARY outcome

Timeframe: 5-10 minutes Postdose

Population: Per-protocol population

Mean difference in percentage signal intensity enhancement on postdose T1-weighted SE/FSE images (ProHance - Gadovist/Gadavist)

Outcome measures

Measure	Reader 1 n=191 Lesions Paired exams reviewed by Reader 1	Reader 2 n=133 Lesions Paired exams reviewed by Reader 2	Reader 3 n=159 Lesions Paired exams reviewed by Reader 3	Reader 2 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg	Reader 3 - ProHance MRI after ProHance 0.1 mmol/kg	Reader 3 - Gadovist/Gadavist MRI after Gadovist/Gadavist 0.1 mmol/kg
Percentage Signal Intensity Enhancement on Postdose Images	1.06 percentage signal intensity enhancement Standard Deviation 28.61	-2.09 percentage signal intensity enhancement Standard Deviation 29.06	-1.59 percentage signal intensity enhancement Standard Deviation 29.16	—	—	—

SECONDARY outcome

Timeframe: 5-10 minutes Postdose

Population: Per protocol patients with histologically confirmed lesions

Lesion detection rate by contrast agent and reader

Outcome measures

Measure	Reader 1 n=139 Participants Paired exams reviewed by Reader 1	Reader 2 n=139 Participants Paired exams reviewed by Reader 2	Reader 3 n=139 Participants Paired exams reviewed by Reader 3	Reader 2 - Gadovist/Gadavist n=139 Participants MRI after Gadovist/Gadavist 0.1 mmol/kg	Reader 3 - ProHance n=139 Participants MRI after ProHance 0.1 mmol/kg	Reader 3 - Gadovist/Gadavist n=139 Participants MRI after Gadovist/Gadavist 0.1 mmol/kg
Lesion Detection True Positive (Patients)	133 participant exams	135 participant exams	137 participant exams	136 participant exams	136 participant exams	132 participant exams
Lesion Detection False Negative (Pa	6 participant exams	4 participant exams	2 participant exams	3 participant exams	3 participant exams	7 participant exams

SECONDARY outcome

Timeframe: 5-10 minutes Postdose

Population: Subjects with histologically confirmed lesions

Blinded reader assessment of accuracy of tumor characterization (benign/malignant) - patient level assessment

Outcome measures

Measure	Reader 1 n=128 Participants Paired exams reviewed by Reader 1	Reader 2 n=128 Participants Paired exams reviewed by Reader 2	Reader 3 n=128 Participants Paired exams reviewed by Reader 3	Reader 2 - Gadovist/Gadavist n=128 Participants MRI after Gadovist/Gadavist 0.1 mmol/kg	Reader 3 - ProHance n=128 Participants MRI after ProHance 0.1 mmol/kg	Reader 3 - Gadovist/Gadavist n=128 Participants MRI after Gadovist/Gadavist 0.1 mmol/kg
Accuracy for Tumor Characterization Patients with Tumors Correctly Categorized	94 participants	96 participants	106 participants	101 participants	93 participants	83 participants
Accuracy for Tumor Characterization Patients with Tumors Incorrectly Categorized	34 participants	32 participants	22 participants	27 participants	35 participants	45 participants

Adverse Events

Safety Population (ProHance)

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Safety Population (Gadovist/Gadavist)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Safety Population (ProHance) n=222 participants at risk All enrolled patients who received a randomized injection of ProHance	Safety Population (Gadovist/Gadavist) n=216 participants at risk All enrolled patients who received a randomized injection of Gadovist/Gadavist
Gastrointestinal disorders Diarrhea	0.45% 1/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.00% 0/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Gastrointestinal disorders Nausea	1.8% 4/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.46% 1/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Gastrointestinal disorders Vomiting	0.45% 1/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.46% 1/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Gastrointestinal disorders Fatigue	0.00% 0/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.46% 1/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
General disorders Feeling hot	0.45% 1/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.00% 0/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Nervous system disorders Convulsion	0.00% 0/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.46% 1/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Nervous system disorders Dizziness	0.45% 1/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.46% 1/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Nervous system disorders Dysgeusia	1.8% 4/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.46% 1/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Nervous system disorders Headache	0.90% 2/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.46% 1/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Nervous system disorders Lethargy	0.45% 1/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.00% 0/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Nervous system disorders Migraine	0.45% 1/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.00% 0/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Nervous system disorders Paresthesia	0.00% 0/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.46% 1/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Psychiatric disorders Anxiety	0.00% 0/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.46% 1/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Psychiatric disorders Mood altered	0.00% 0/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.46% 1/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Respiratory, thoracic and mediastinal disorders Cough	0.90% 2/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.00% 0/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Respiratory, thoracic and mediastinal disorders Dyspnea	0.45% 1/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.00% 0/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Respiratory, thoracic and mediastinal disorders Orophanyngeal pain	0.00% 0/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.46% 1/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Skin and subcutaneous tissue disorders Pruritus	0.45% 1/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.00% 0/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Skin and subcutaneous tissue disorders Rash	0.45% 1/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.00% 0/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Skin and subcutaneous tissue disorders Urticaria	0.45% 1/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.00% 0/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated
Vascular disorders Vascular rupture	0.45% 1/222 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated	0.00% 0/216 • Up to 24 hours after contrast media injection All adverse events collected were categorized using MedDRA 16.1 and tabulated

Additional Information

Gianpaolo Pirovano, MD

Executive Director, MRI

Phone: 609-514-2226

Email: gianpaolo.pirovano@diag.bracco.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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
• Publication restrictions are in place

Restriction type: OTHER