REMIND: Efficacy Evaluation of Dotarem®-Enhanced MRI Compared to Gadovist®/Gadavist®-Enhanced MRI in the Diagnosis of Brain Tumors

• Sponsor: Guerbet (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02034708
• Collaborator: (none)
• Enrollment: 279
• Locations: 32
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate non-inferiority of Dotarem®-enhanced MRI as compared to Gadovist®/ Gadavist®-enhanced MRI in the diagnosis of brain tumors in terms of overall lesion visualization and characterization (off-site assessment).

270 patients will be randomized between 2 arms defining the sequence of administration of the contrast agents at the dose of 0.1mmol/kg, with a minimum of 48 hours and a maximum of 14 days in between.

Each patient will, therefore, receive two MRI during his/her participation in the study.

The two arms consist in :

• Dotarem® in the first MRI, then Gadovist®/Gadavist® in the second MRI.

• Gadovist®/Gadavist® in the first MRI, then Dotarem® in the second MRI.

Contrast-enhanced MRIs will be performed on 1.5 or 3 Tesla systems.

MRI examinations will be evaluated centrally by blinded independent readers for the main evaluation criterion.

Condition or Disease	Intervention/Treatment	Phase
Primary Brain Tumor	Drug: Dotarem®; Drug: Gadovist®/Gadavist®	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 279 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Intra-individual Cross-over Efficacy Evaluation of Dotarem®-Enhanced MRI Compared to Gadovist®/ Gadavist®-Enhanced MRI in the Diagnosis of Brain Tumors
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dotarem®/Gadovist® Dotarem®-enhanced MRI, then Gadovist®/Gadavist®-enhanced MRI	Drug: Dotarem®; Dotarem® 0.1 mmoL/kg (0.2 mL/kg), intravenous (I.V.) bolus.; Drug: Gadovist®/Gadavist®; Gadovist®/Gadavist®, 0.1mmol/kg (0.1mL/kg), intravenous (I.V.) bolus.
Experimental: Gadovist®/Dotarem® Gadovist®/Gadavist®-enhanced MRI then Dotarem® enhanced MRI	Drug: Dotarem®; Dotarem® 0.1 mmoL/kg (0.2 mL/kg), intravenous (I.V.) bolus.; Drug: Gadovist®/Gadavist®; Gadovist®/Gadavist®, 0.1mmol/kg (0.1mL/kg), intravenous (I.V.) bolus.

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With Overall Lesion Visualization and Characterization Scored as Good or Excellent [Up to 15 days after randomization]

   Overall lesion visualization and characterization, based on assessment of the primary or largest lesion if there is more than one lesion present, was assessed by 3 independent off-site readers on a 4-point scale: 0. Poor: does not allow adequate visualization and characterization of the lesion; 1. Fair: allows partial visualization and characterization of the lesion ; 2. Good: allows adequate visualization and characterization of the lesion; 3. Excellent: allows excellent visualization and characterization of the lesion.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female or male adult patient (patient having reached legal majority age)

• Patient with known or highly suspected primary intracranial tumors (intra-axial or extra-axial) detected by previous CT or MRI examination who are scheduled to undergo a routine contrast-enhanced MRI

• Female patient must have effective contraception throughout the study and must have a negative urine pregnancy test at inclusion, or be surgically sterilized, or post-menopausal (minimum 12 months of amenorrhea)

• Patient having provided his/her written informed consent to participate in the trial prior to any study-related procedure being conducted

• Patient with national health insurance (according to local regulatory requirements)

Exclusion Criteria:

• Patient with rapidly evolving brain tumor that could change in appearance between the time of the two study MRI examinations.

• Patient undergoing current or recent treatment within past 6 weeks or scheduled for any treatment that could results in changes of lesion appearance between the two study examinations. This would include, but not restricted to, the following: current or recent radiation therapy, surgery, starting or recent chemotherapy.

• Patient with a contraindication to MRI (e.g., pacemaker, aneurysm clip, severe claustrophobia, infusion pumps, cochlear implants metallic or others according to the imaging site standard practice)

• Patient with known severely impaired renal function (defined as eGFR MDRD< 30 ml/min/1.73m2)

• Patient with known Class III/IV congestive heart failure according to the New York Heart Association classification

• Patient with known severe adverse drug reaction or contraindication to Gadolinium-Based Contrast Agent

• Patient having received any contrast agent within 48 hours prior to first study contrast agent injection scheduled for the study and patient expected to receive any other contrast agent within 24 hours of the last study contrast agent injection

• Patient presenting with any condition which, based on the investigator's clinical judgment, would prevent the patient from completing all trial assessments and visits

• Patient under guardianship and/or unable or unwilling to cooperate with the requirements of this trial

• Pregnant or breast feeding female patient

• Patient already included in this trial

• Patient included in another clinical trial involving an IMP within 30 days before the first investigational contrast agent injection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States
2	University of Arizona Medical Center	Tucson	Arizona	United States	AZ 85724
3	Cedars-Sinai Medical Center	Los Angeles	California	United States
4	Yale University School Of Medicine	New Haven	Connecticut	United States
5	Infinity Clinical Research, LLC	Hollywood	Florida	United States	FL 33021
6	University of Michigan Health System	Ann Arbor	Michigan	United States
7	Quest Research Institute	Farmington Hills	Michigan	United States
8	Spectrum Health	Grand Rapids	Michigan	United States
9	Washington University	St. Louis	Missouri	United States
10	Winthrop University Hospital Clinical Trials Center	Mineola	New York	United States	NY 11501
11	Temple University Hospital	Philadelphia	Pennsylvania	United States
12	MUSC (Medical University of South Carolina)	Charleston	South Carolina	United States
13	UVM MRI Center for Biomedical Imaging	Burlington	Vermont	United States
14	University of Washington Medical Center	Seattle	Washington	United States
15	Fundacion Abood Shaio	Bogota		Colombia
16	Fundacion Cardioinfantil Instituto de Cardiologia	Bogota		Colombia
17	Instituto Nacional de Cancerologia	Bogota		Colombia
18	Centro Medico Imbanaco	Cali		Colombia
19	Fundacion Instituto de Alta Tecnologia Medica de Antioquia IATM	Medellin		Colombia
20	Hospital Pablo Tobon Uribe	Medellin		Colombia
21	Chungbuk National University	Cheongju-si	Chungcheongbuk-do	Korea, Republic of	361-711
22	Chonbuk national Univ Hosp	Jeonju-si	Jeollabuk-do	Korea, Republic of	561-712
23	Seoul St.Mary Hospital	Seoul	Seocho-gu	Korea, Republic of	137-701
24	Asan medical center	Seoul	Songpa-Gu	Korea, Republic of	138-736
25	Ajou University Hospital	Suwon		Korea, Republic of
26	Morales Vargas Centro de Investigación S.C.	Leon	Guanajuato	Mexico	37000
27	Centro Neurologico ABC	Mexico	Mexico Distrito Federal	Mexico	5300
28	Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo Leon	Mexico	64020
29	Winsett Rethman S.A. de C.V.	Monterrey	Nuevo León	Mexico
30	Hospital CIMA	Chihuahua		Mexico	31238
31	Centro Regiomontano de Investigacion S.C.	Monterrey		Mexico
32	Clinical Research Institute S.C.	Tlanepantla		Mexico

Sponsors and Collaborators

• Guerbet

Investigators

• Study Chair: Kenneth Maravilla, MD, University of Washington Medical Center, Seattle, USA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Guerbet
• ClinicalTrials.gov Identifier: NCT02034708
• Other Study ID Numbers: DGD-44-058
• First Posted: Jan 13, 2014
• Last Update Posted: Dec 30, 2016
• Last Verified: Nov 1, 2016

• Keywords provided by Guerbet: Primary brain tumor
• Additional relevant MeSH terms: Brain Neoplasms

Study Results

Participant Flow

Recruitment Details	Adult patients with known or highly suspected primary intracranial tumors and scheduled for a Dotarem®-enhanced MRI were recruited in 27 active centers in 4 countries (Colombia, South Korea, Mexico and United States) from June 2014 to September 2015.
Pre-assignment Detail	279 patients signed an informed consent for the study and therefore were considered as included. From these 279 patients, 11 did not receive any injection : 4 for consent withdrawn, 3 for deviation from plan specified in the protocol, 2 for adverse events, 1 at the investigator's discretion and 1 for other reason.

Arm/Group Title	Dotarem®/Gadovist®	Gadovist®/Dotarem®
Arm/Group Description	Dotarem®-enhanced MRI, then Gadovist®/Gadavist®-enhanced MRI Dotarem®: 0.1 mmoL/kg (0.2 mL/kg), intravenous (I.V.) bolus. Gadovist®/Gadavist®: 0.1mmol/kg (0.1mL/kg), intravenous (I.V.) bolus.	Gadovist®/Gadavist®-enhanced MRI then Dotarem® enhanced MRI Dotarem®: 0.1 mmoL/kg (0.2 mL/kg), intravenous (I.V.) bolus. Gadovist®/Gadavist®: 0.1mmol/kg (0.1mL/kg), intravenous (I.V.) bolus.
Period Title: First Contrast Agent Injection (1 Day)
STARTED	138	130
COMPLETED	138	130
NOT COMPLETED	0	0
Period Title: First Contrast Agent Injection (1 Day)
STARTED	138	130
COMPLETED	129	120
NOT COMPLETED	9	10
Period Title: First Contrast Agent Injection (1 Day)
STARTED	129	120
COMPLETED	129	120
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Dotarem®/Gadovist®	Gadovist®/Dotarem®	Total
Arm/Group Description	Dotarem®-enhanced MRI, then Gadovist®/Gadavist®-enhanced MRI Dotarem®: 0.1 mmoL/kg (0.2 mL/kg), intravenous (I.V.) bolus. Gadovist®/Gadavist®: 0.1mmol/kg (0.1mL/kg), intravenous (I.V.) bolus.	Gadovist®/Gadavist®-enhanced MRI then Dotarem® enhanced MRI Dotarem®: 0.1 mmoL/kg (0.2 mL/kg), intravenous (I.V.) bolus. Gadovist®/Gadavist®: 0.1mmol/kg (0.1mL/kg), intravenous (I.V.) bolus.	Total of all reporting groups
Overall Participants	138	130	268
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.9 (15.2)	54.4 (15.1)	53.6 (15.1)
Gender (Count of Participants)
Female	87 63%	85 65.4%	172 64.2%
Male	51 37%	45 34.6%	96 35.8%
Region of Enrollment (participants) [Number]
Colombia	16 11.6%	16 12.3%	32 11.9%
United States	46 33.3%	40 30.8%	86 32.1%
Korea, Republic of	24 17.4%	23 17.7%	47 17.5%
Mexico	52 37.7%	51 39.2%	103 38.4%
Body Mass Index (kg per square metre) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg per square metre]	27.71 (5.35)	27.62 (5.23)	27.66 (5.28)

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Overall Lesion Visualization and Characterization Scored as Good or Excellent
Description	Overall lesion visualization and characterization, based on assessment of the primary or largest lesion if there is more than one lesion present, was assessed by 3 independent off-site readers on a 4-point scale: 0. Poor: does not allow adequate visualization and characterization of the lesion; 1. Fair: allows partial visualization and characterization of the lesion ; 2. Good: allows adequate visualization and characterization of the lesion; 3. Excellent: allows excellent visualization and characterization of the lesion.
Time Frame	Up to 15 days after randomization

Outcome Measure Data

Analysis Population Description

Patients with at least one valid assessment of the primary outcome and without major protocol deviation

Arm/Group Title	Gadovist® (Reader 1)	Dotarem® (Reader 1)	Gadovist® (Reader 2)	Dotarem® (Reader 2)	Gadovist® (Reader 3)	Dotarem® (Reader 3)
Arm/Group Description	Patients who received Gadovist® Results for reader 1	Patients who received Dotarem® Results for reader 1	Patients who received Gadovist® Results for reader 2	Patients who received Dotarem® Results for reader 2	Patients who received Gadovist® Results for reader 3	Patients who received Dotarem® Results for reader 3
Measure Participants	234	234	234	234	234	234
Number [percentage of patients]	94.0	96.2	93.2	90.6	99.6	100.0

Adverse Events

Time Frame	From patient inclusion up to 30 min after last contrast agent injection
Arm/Group Title	Dotarem®		Gadovist®		Total
Arm/Group Description	Patients who received Dotarem®		Patients who received Gadovist®		Patients who received at least one injection of contrast agent
All Cause Mortality
	Dotarem®		Gadovist®		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Dotarem®		Gadovist®		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/258 (0.4%)		0/259 (0%)		1/268 (0.4%)
General disorders
Aggravation of existing disorder	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
Nervous system disorders
Coma	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Dotarem®		Gadovist®		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/258 (16.3%)		44/259 (17%)		63/268 (23.5%)
Cardiac disorders
Bradycardia	0/258 (0%)	0	1/259 (0.4%)	1	1/268 (0.4%)	1
Eye disorders
Eye swelling	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
Gastrointestinal disorders
Nausea	2/258 (0.8%)	2	3/259 (1.2%)	3	5/268 (1.9%)	5
Infrequent bowel movements	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
Vomiting	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
General disorders
Injection site pain	12/258 (4.7%)	12	12/259 (4.6%)	13	20/268 (7.5%)	25
Medical device pain	15/258 (5.8%)	15	17/259 (6.6%)	17	17/268 (6.3%)	32
Injection site coldness	1/258 (0.4%)	1	1/259 (0.4%)	1	2/268 (0.7%)	2
Injection site paraesthesia	2/258 (0.8%)	2	1/259 (0.4%)	1	2/268 (0.7%)	3
Catheter site related reaction	0/258 (0%)	0	1/259 (0.4%)	1	1/268 (0.4%)	1
Chest pain	0/258 (0%)	0	1/259 (0.4%)	1	1/268 (0.4%)	1
Drug ineffective	0/258 (0%)	0	1/259 (0.4%)	1	1/268 (0.4%)	1
Feeling cold	0/258 (0%)	0	1/259 (0.4%)	1	1/268 (0.4%)	1
Feeling hot	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
Injection site erythema	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
Injection site inflammation	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
Injection site rash	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
Injection site reaction	1/258 (0.4%)	1	1/259 (0.4%)	1	1/268 (0.4%)	2
Infections and infestations
Pharyngitis	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
Investigations
Blood pressure increased	0/258 (0%)	0	2/259 (0.8%)	2	2/268 (0.7%)	2
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/258 (0.4%)	1	1/259 (0.4%)	1	2/268 (0.7%)	2
Back pain	0/258 (0%)	0	1/259 (0.4%)	1	1/268 (0.4%)	1
Neck pain	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
Nervous system disorders
Headache	4/258 (1.6%)	4	3/259 (1.2%)	3	7/268 (2.6%)	7
Dizziness	2/258 (0.8%)	2	4/259 (1.5%)	4	5/268 (1.9%)	6
Paraesthesia	2/258 (0.8%)	2	0/259 (0%)	0	2/268 (0.7%)	2
Hypoaesthesia	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1
Skin and subcutaneous tissue disorders
Dermatosis	0/258 (0%)	0	1/259 (0.4%)	1	1/268 (0.4%)	1
Rash	0/258 (0%)	0	1/259 (0.4%)	1	1/268 (0.4%)	1
Vascular disorders
Hot flush	1/258 (0.4%)	1	0/259 (0%)	0	1/268 (0.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Each investigator agrees not to publish/present the results of the study main criterion involving only the patients included in his/her center. Publications on specific topics can be performed only after main publication.The sponsor can review the publication at least 30 days before the submission to the scientific review and any abstract project at least 10 working days before submission to the congress scientific committee. The sponsor can require changes to the publication or the abstract.