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This trial aimed to evaluate the Efficacy and Safety of gadopiclenol for Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)
The purpose of this trial was to evaluate a new gadolinium-based contrast agent (GBCA) gadopiclenol injection for Central Nervous System (CNS) lesion detection and visualization by conventional steady-state CNS imaging.
This is a multi-center, international, prospective, double-blind, randomized, controlled, cross-over with comparator trial in male and female patients presenting with known or highly suspected CNS lesion(s) with focal areas of disrupted Blood Brain Barrier (BBB) (e.g., primary and secondary tumors) who are scheduled to undergo a routine contrast-enhanced Magnetic Resonance Imaging (MRI) of the CNS.
This trial was conducted in 33 centers worldwide.
During the course of the trial, two MRIs were obtained from each patient: one unenhanced and gadopiclenol-enhanced MRI; and one unenhanced and gadobutrol-enhanced MRI. MRI evaluations were performed by on-site investigators and three independent off-site blinded readers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| gadopiclenol-enhanced MRI then gadobutrol-enhanced MRI | Other | cross-over design. each patient will receive gadopiclenol for the first MRI and gadobutrol for the second MRI |
|
| gadobutrol-enhanced MRI then gadopiclenol-enhanced MRI | Other | cross-over design. each patient will receive gadobutrol for the first MRI and gadopiclenol for the second MRI |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| gadopiclenol | Drug | single intravenous (IV) bolus injection at a rate of 2ml/second |
|
| Measure | Description | Time Frame |
|---|---|---|
| Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | The lesion visualization (per patient) was based on 3 co-primary criteria on marching lesions: border delineation, internal morphology and degree of contrast enhancement, assessed on the images acquired during the MRI performed with gadopiclenol by 3 independent readers. The independent blinded reader recorded each of the 3 co-primary criteria for up to 3 most representative lesions, using a 4-point scale (1 = poor [internal morphology] or none [border delineation, contrast enhancement], 2 = moderate, 3 = good, 4 = excellent). The mean of scores for each patient and for each co-criterion was calculated as follows: Mean of scores = score of lesion 1 + score of lesion 2 (if any) + score of lesion 3 (if any) divided by the number of lesions, ranged from 1 to 4. The difference in mean scores on matching lesions between Paired [unenhanced and contrast-enhanced] images and Pre-contrast [unenhanced] images was calculated for each of the 3 co-primary criteria and for each reader. | At first MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 1. At second MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 2, performed 2-14 days after gadobutrol-enhanced MRI. |
| Measure | Description | Time Frame |
|---|---|---|
| Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | The lesion visualization (per patient) was based on 3 co-primary criteria: border delineation, internal morphology and degree of contrast enhancement, assessed on the images performed with gadopiclenol and images performed with gadobutrol by 3 independent readers. The independent blinded reader recorded each of the 3 co-primary criteria for up to 3 most representative lesions, using a 4-point scale (1 = poor [internal morphology] or none [border delineation, contrast enhancement], 2 = moderate, 3 = good, 4 = excellent). The mean of scores for each patient and for each of the 3 lesion visualization co-criteria was calculated as follows: Mean of scores = score of lesion 1 + score of lesion 2 (if any) + score of lesion 3 (if any) divided by the number of lesions, ranged from 1 to 4. The difference in mean scores on matching lesions between gadopiclenol scores mean and gadobutrol scores mean was calculated for each of the 3 co-primary criteria and for each reader. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lorie Loevner, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ASCLEPES Research Centers | Panorama City | California | 91402 | United States | ||
| University of Connecticut Health Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36729404 | Result | Loevner LA, Kolumban B, Hutoczki G, Dziadziuszko K, Bereczki D, Bago A, Pichiecchio A. Efficacy and Safety of Gadopiclenol for Contrast-Enhanced MRI of the Central Nervous System: The PICTURE Randomized Clinical Trial. Invest Radiol. 2023 May 1;58(5):307-313. doi: 10.1097/RLI.0000000000000944. Epub 2022 Dec 19. |
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Among the 260 screened patients, 4 were screen failed. A total of 256 patients were randomized (128 in each arm), of whom 6 discontinued the trial before receiving the first contrast agent. Then 250 patients (125 in each arm) received the first contrast agent and underwent the first MRI (First MRI Period). After a washout period of 2-14 days (Washout Period), 242 patients (120 in the Arm 1 and 122 in the Arm 2) received the second contrast agent and underwent the second MRI (Second MRI Period).
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: Gadopiclenol-enhanced MRI for First MRI and Gadobutrol-enhanced MRI for Second MRI | Cross-over study design For each patient in this Arm, he (she) performed the first contrast-enhanced MRI with gadopiclenol as contrast agent (First MRI Period). After a washout period of 2-14 days (Washout Period), the patient performed the second contrast-enhanced MRI with gadobutrol as contrast agent (Second MRI Period). For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadopiclenol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadobutrol-enhanced MR images obtained in the second MRI Examination Period. Gadopiclenol: single intravenous (IV) bolus injection at a rate of 2ml/second Gadobutrol 1Mmol/mL Solution for Injection Vial: single intravenous (IV) bolus injection at a rate of 2ml/second |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First MRI Examination |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 20, 2018 | Oct 24, 2022 |
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| Gadobutrol 1Mmol/mL Solution for Injection Vial | Drug | single intravenous (IV) bolus injection at a rate of 2ml/second |
|
| At each of two MRI examinations with an interval of 2-14 days between 2 MRI examinations |
| Farmington |
| Connecticut |
| 06030 |
| United States |
| Northwestern Memorial Hospital | Chicago | Illinois | 60611 | United States |
| Northwest Neurology, Ltd. | Rolling Meadows | Illinois | 600008 | United States |
| University of Missouri Hospital and Clinic | Columbia | Missouri | 65212 | United States |
| University Of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| South Carolina Clinical & Translational Research (SCTR) Institute | Charleston | South Carolina | 29425 | United States |
| University Of Washington - Medical Center | Seattle | Washington | 98195 | United States |
| ZNA Middelheim | Antwerp | Belgium |
| UZ Brussel - Campus Jette | Brussels | 1090 | Belgium |
| CHRU - Hôpital Roger Salengro - Neurologie | Lille | France |
| Centre Hospitalier Sainte-Anne | Paris | 75014 | France |
| CHU La Miletrie | Poitiers | France |
| CHRU Strasbourg Hôpital de Hautepierre | Strasbourg | 67098 | France |
| Uniklinik Mannheim | Mannheim | 68167 | Germany |
| Semmelweis Egyetem - Neurology | Budapest | 1083 | Hungary |
| Orszagos Klinikai Idegtudomanyi Intezet | Budapest | 1145 | Hungary |
| Debreceni Egyetem Klinikai Kozpont | Debrecen | Hungary |
| Pecsi Tudomanyegyetem Klinikai Kozpont - Idegsebeszeti Klinika | Pécs | Pécs | Hungary |
| Szegedi Tudomanyegyetem AOK | Szeged | 6725 | Hungary |
| ASL 1 Abruzzo Avezzano-Sulmona-L'Aquila, Ospedale Regionale San Salvatore | L’Aquila | Italy |
| Fondazione I.R.C.C.S. C.Mondino | Pavia | 27100 | Italy |
| Istituto Neurologico Mediterraneo-Neuromed, I.R.C.C.S. | Pozzilli | 86077 | Italy |
| Azienda Sanitaria Universitaria Integrata di Trieste-PO Cattinara | Trieste | 34149 | Italy |
| Axis Heilsa S. de R.L. de C.V. (Althian) | Monterrey | 64060 | Mexico |
| Clinical Research Institute S.C | Tlalnepantla | 54055 | Mexico |
| Uniwersyteckie Centrum Kliniczne w Gdańsku, Zakład Radiologii | Gdansk | 80-214 | Poland |
| Konkuk University Medical Center | Seoul | 05030 | South Korea |
| Asan Medical Center | Seoul | 5505 | South Korea |
| Hospital del Mar | Barcelona | 08003 | Spain |
| M.D. Anderson Cancer Center Madrid | Madrid | 28033 | Spain |
| Hospital Clínico San Carlos | Madrid | 28040 | Spain |
| Taipei Veterans General Hospital | Taipei | 11217 | Taiwan |
| FG001 | Arm 2: Gadobutrol-enhanced MRI for First MRI and Gadopiclenol-enhanced MRI for Second MRI | Cross-over study design For each patient in this Arm, he (she) performed the first contrast-enhanced MRI with gadobutrol as contrast agent (First MRI Period). After a washout period of 2-14 days (Washout Period), the patient performed the second contrast-enhanced MRI with gadopiclenol as contrast agent (Second MRI Period). For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadobutrol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadopiclenol-enhanced MR images obtained in the second MRI Examination Period. Gadobutrol 1Mmol/mL Solution for Injection Vial: single intravenous (IV) bolus injection at a rate of 2ml/second Gadopiclenol: single intravenous (IV) bolus injection at a rate of 2ml/second |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Washout |
|
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| Second MRI Examination |
|
The analysis was based on participants. For the primary analysis to demonstrate the superiority of gadopiclenol-enhanced MRI compared to unenhanced MRI, the analysis population was patients who had both Pre (unenhanced) and Paired (combined unenhanced and contrast-enhanced) images with gadopiclenol assessable for primary criteria for at least one matching lesion for at least one off-site reader: 119 patients of Arm 1 who performed first MRI and 120 patients of Arm 2 who performed second MRI.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1: Gadopiclenol-enhanced MRI for First MRI and Gadobutrol-enhanced MRI for Second MRI | Cross-over study design For Arm 1, the patient performed the first contrast-enhanced MRI with gadopiclenol as contrast agent. After a washout period of 2-14 days, the patient performed the second contrast-enhanced MRI with gadobutrol as contrast agent. For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadopiclenol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadobutrol-enhanced MR Images obtained in the Second MRI Examination Period . |
| BG001 | Arm 2: Gadobutrol-enhanced MRI for First MRI and Gadopiclenol-enhanced MRI for Second MRI | Cross-over study design For Arm 2, the patient performed the first contrast-enhanced MRI with gadobutrol as contrast agent. After a washout period of 2-14 days, the patient performed the second contrast-enhanced MRI with gadopiclenol as contrast agent. For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadobutrol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadopiclenol-enhanced MR images obtained in the Second MRI Examination Period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Weight | Mean | Standard Deviation | Kg |
|
| 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 | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | The lesion visualization (per patient) was based on 3 co-primary criteria on marching lesions: border delineation, internal morphology and degree of contrast enhancement, assessed on the images acquired during the MRI performed with gadopiclenol by 3 independent readers. The independent blinded reader recorded each of the 3 co-primary criteria for up to 3 most representative lesions, using a 4-point scale (1 = poor [internal morphology] or none [border delineation, contrast enhancement], 2 = moderate, 3 = good, 4 = excellent). The mean of scores for each patient and for each co-criterion was calculated as follows: Mean of scores = score of lesion 1 + score of lesion 2 (if any) + score of lesion 3 (if any) divided by the number of lesions, ranged from 1 to 4. The difference in mean scores on matching lesions between Paired [unenhanced and contrast-enhanced] images and Pre-contrast [unenhanced] images was calculated for each of the 3 co-primary criteria and for each reader. | Full Analysis Set (FAS) included a total of 239 patients who had both Pre and Paired images with gadopiclenol assessable for primary criteria for at least one matching lesion for at least one off-site reader: 119 patients in the Arm 1 for whom gadopiclenol-enhanced MRI was performed as first MRI, and 120 patients in the Arm 2 for whom gadopiclenol-enhanced MRI was performed as second MRI. The analysis was based on participants (per patient). | Posted | Least Squares Mean | Standard Error | mean of a score (on a scale) per patient | At first MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 1. At second MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 2, performed 2-14 days after gadobutrol-enhanced MRI. |
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| Secondary | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | The lesion visualization (per patient) was based on 3 co-primary criteria: border delineation, internal morphology and degree of contrast enhancement, assessed on the images performed with gadopiclenol and images performed with gadobutrol by 3 independent readers. The independent blinded reader recorded each of the 3 co-primary criteria for up to 3 most representative lesions, using a 4-point scale (1 = poor [internal morphology] or none [border delineation, contrast enhancement], 2 = moderate, 3 = good, 4 = excellent). The mean of scores for each patient and for each of the 3 lesion visualization co-criteria was calculated as follows: Mean of scores = score of lesion 1 + score of lesion 2 (if any) + score of lesion 3 (if any) divided by the number of lesions, ranged from 1 to 4. The difference in mean scores on matching lesions between gadopiclenol scores mean and gadobutrol scores mean was calculated for each of the 3 co-primary criteria and for each reader. | Per-Protocol Set (PPS) analysis population including a total of 236 patients (117 patients of Arm 1 and 119 patients of Arm 2) with no major protocol deviation who have Paired (combined unenhanced and contrast-enhanced) images for both gadopiclenol and gadobutrol assessable for this secondary outcome mesure for at least one matching lesion for at least one off-site reader. The analysis was based on participants (per patient). | Posted | Least Squares Mean | Standard Error | mean of a score (on a scale) per patient | At each of two MRI examinations with an interval of 2-14 days between 2 MRI examinations |
|
Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Gadopiclenol | AEs reported after MRI with gadopiclenol | 0 | 247 | 0 | 247 | 36 | 247 |
| EG001 | Gadobutrol | AEs reported after MRI with gadobutrol | 1 | 245 | 1 | 245 | 42 | 245 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| General Physical Health Deterioration | General disorders | MedDRA dictionary | Systematic Assessment | Not related to contrast-agent |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site pain | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Injection site bruising | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Injection site coldness | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Injection site warmth | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Injection site haematoma | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Injection site haemorrhage | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Injection site paraesthesia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Vessel puncture site haemorrhage | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Drug ineffective | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Feeling hot | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Injection site discomfort | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Injection site extravasation | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Injection site hypoaesthesia | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Injection site oedema | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Partial seizures | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 23.1 | Systematic Assessment |
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| Blood phosphorus decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
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| Neutrophil count increased | Investigations | MedDRA 23.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Paraesthesia oral | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Myofascial pain syndrome | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Incorrect dose administered | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Claustrophobia | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Sleep disorder | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Anaemia macrocytic | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Scleral haemorrhage | Eye disorders | MedDRA 23.1 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Pallor | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jing Hao, MD, Global Head of Medical Affairs & Clinical Development | Guerbet | +33 (0) 1 45 91 50 00 | jing.hao@guerbet.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 9, 2020 | Oct 24, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000656634 | gadopiclenol |
| C090600 | gadobutrol |
| D012996 | Solutions |
| ID | Term |
|---|---|
| D004364 | Pharmaceutical Preparations |
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| Withdrawal by Subject |
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| Other reason |
|
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Belgium |
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| Hungary |
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| United States |
|
| Taiwan |
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| Poland |
|
| Italy |
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| Mexico |
|
| France |
|
| Germany |
|
| Spain |
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| Border delineation - Reader 3 |
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| Internal morphology - Reader 1 |
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| Internal morphology - Reader 2 |
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| Internal morphology - Reader 3 |
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| Contrast enhancement - Reader 1 |
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| Contrast enhancement - Reader 2 |
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| Contrast enhancement - Reader 3 |
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| Superiority |
| Criterion: Border delineation; Reader 2. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously. | t-test, 2 sided | <.0001 | To demonstrate the superiority, a statistically significant (one-sided p-value ≤0.025) positive difference in mean scores in border delineation, internal morphology and degree of contrast enhancement of lesions had to be met for 2 out of 3 readers. | Mean Difference (Final Values) | 1.90 | Standard Error of the Mean | 0.05 | 2-Sided | 95 | 1.81 | 2.00 | Superiority |
| Criterion: Border delineation; Reader 3. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously. | t-test, 2 sided | <.0001 | To demonstrate the superiority, a statistically significant (one-sided p-value ≤0.025) positive difference in mean scores in border delineation, internal morphology and degree of contrast enhancement of lesions had to be met for 2 out of 3 readers. | Mean Difference (Final Values) | 1.36 | Standard Error of the Mean | 0.04 | 2-Sided | 95 | 1.29 | 1.44 | Superiority |
| Criterion: Internal morphology; Reader 1. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously. | t-test, 2 sided | <.0001 | To demonstrate the superiority, a statistically significant (one-sided p-value ≤0.025) positive difference in mean scores in border delineation, internal morphology and degree of contrast enhancement of lesions had to be met for 2 out of 3 readers. | Mean Difference (Final Values) | 2.26 | Standard Error of the Mean | 0.03 | 2-Sided | 95 | 2.20 | 2.33 | Superiority |
| Criterion: Internal morphology; Reader 2. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously. | t-test, 2 sided | <.0001 | To demonstrate the superiority, a statistically significant (one-sided p-value ≤0.025) positive difference in mean scores in border delineation, internal morphology and degree of contrast enhancement of lesions had to be met for 2 out of 3 readers. | Mean Difference (Final Values) | 1.77 | Standard Error of the Mean | 0.04 | 2-Sided | 95 | 1.69 | 1.85 | Superiority |
| Criterion: Internal morphology; Reader 3. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously. | t-test, 2 sided | <.0001 | To demonstrate the superiority, a statistically significant (one-sided p-value ≤0.025) positive difference in mean scores in border delineation, internal morphology and degree of contrast enhancement of lesions had to be met for 2 out of 3 readers. | Mean Difference (Final Values) | 1.96 | Standard Error of the Mean | 0.05 | 2-Sided | 95 | 1.85 | 2.06 | Superiority |
| Criterion: Contrast enhancement; Reader 1. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously. | t-test, 2 sided | <.0001 | To demonstrate the superiority, a statistically significant (one-sided p-value ≤0.025) positive difference in mean scores in border delineation, internal morphology and degree of contrast enhancement of lesions had to be met for 2 out of 3 readers. | Mean Difference (Final Values) | 2.77 | Standard Error of the Mean | 0.04 | 2-Sided | 95 | 2.69 | 2.85 | Superiority |
| Criterion: Contrast enhancement - Reader 2. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously. | t-test, 2 sided | <.0001 | To demonstrate the superiority, a statistically significant (one-sided p-value ≤0.025) positive difference in mean scores in border delineation, internal morphology and degree of contrast enhancement of lesions had to be met for 2 out of 3 readers. | Mean Difference (Final Values) | 2.58 | Standard Error of the Mean | 0.05 | 2-Sided | 95 | 2.49 | 2.67 | Superiority |
| Criterion: Contrast enhancement; Reader 3. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously. | t-test, 2 sided | <.0001 | To demonstrate the superiority, a statistically significant (one-sided p-value ≤0.025) positive difference in mean scores in border delineation, internal morphology and degree of contrast enhancement of lesions had to be met for 2 out of 3 readers. | Mean Difference (Final Values) | 2.90 | Standard Error of the Mean | 0.03 | 2-Sided | 95 | 2.84 | 2.95 | Superiority |
Analysis included 236 patients (117 patients in the Arm 1 and 119 patients in the Arm 2) with no major protocol deviation who have Paired (combined unenhanced and contrast-enhanced) images for both gadopiclenol and gadobutrol assessable for this secondary outcome mesure for at least one matching lesion for at least one off-site reader:
The analysis was based on participants (per patient).
The 236 patients with gadopiclenol Paired images are the same patients with gadobutrol Paired images.
| OG001 | Patients With Gadobutrol Paired Images | Analysis included 236 patients (117 patients in the Arm 1 and 119 patients in the Arm 2) with no major protocol deviation who have Paired (combined unenhanced and contrast-enhanced) images for both gadopiclenol and gadobutrol assessable for this secondary outcome mesure for at least one matching lesion for at least one off-site reader: The analysis was based on participants (per patient). The 236 patients with gadobutrol Paired images are the same patients with gadopiclenol Paired images. |
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