Isovue in Peripheral Digital Subtraction Angiography (DSA)

• Sponsor: Bracco Diagnostics, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01075217
• Collaborator: (none)
• Enrollment: 174
• Location: 1
• Arms: 2
• Duration (Months): 20
• Patients Per Site Per Month: 8.7

Study Details

Study Description

Brief Summary

No significant differences is expected in observed motion artifacts, heat or pain reported during peripheral DSA performed for diagnostic and/or endovascular therapeutic purposes.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Arterial Occlusive Disease	Drug: iopamidol; Drug: iodixanol	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 174 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: A Phase IV Multi-Center Study to Compare ISOVUE -250 and VISIPAQUE 270 for Motion Artifact and Pain in Peripheral Digital Subtraction Angiography (DSA)
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Isovue 250 (iopamidol)	Drug: iopamidol; Participants received at least one intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).; Other Names: Other name: Isovue 250
Active Comparator: Visipaque 270 (iodixanol)	Drug: iodixanol; Participants received at least one intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).; Other Names: Other name: Visipaque 270

Outcome Measures

Primary Outcome Measures

1. Level of Pain/Heat in the Lower Extremities Scored by the Participants on the Visual Analog Scale (VAS) Following Intra-arterial Administration of ISOVUE-250 or VISIPAQUE 270 in Peripheral DSA [immediately after administration of agent using a power injector for the administration]

   The 10-centimeter Pain VAS was completed by the Group 1 patients to assess his/her pain level (not scoring heat separately from pain) in the lower extremity of interest. The scale was 0 to 10 cm, with the left end (0 cm)of the scale indicating no pain and the right end (10 cm) of the scale indicating the worst pain. The 10-centimeter Pain VAS (excluding Heat assessment, which was separately assessed) was completed by the Group 2 patients to assess his/her pain level in the lower extremity of interest. The scale was 0 to 10 cm, with the left end (0 cm)of the scale indicating no pain and the right end (10 cm) of the scale indicating the worst pain. Group 1 completed the Pain VAS (heat not separate from pain). Group 2 completed the Pain VAS for pain only and, separately, the Heat VAS for heat only.

Secondary Outcome Measures

1. Level of Heat in the Lower Extremities Scored by Group 2 as Assessed on the Heat VAS Following Intraarterial Administration of ISOVUE-250 or VISIPAQUE 270 in Peripheral DSA [Immediately after administration of agent using a power injector for the administration]

   The 10-centimeter Heat VAS was completed by the Group 2 patients to assess his/her heat level (separately from pain) in the lower extremity of interest. The scale was 0 to 10 cm, with the left end (0 cm)of the scale indicating no heat and the right end (10 cm) of the scale indicating the worst heat. The Heat VAS was completed by the patient before completing the Pain VAS to assess pain.

2. The Number of Participants With Significant Motion Artifacts (Scores of 3 or 4) Following Intraarterial Administration of ISOVUE-250 or VISIPAQUE 270 in Peripheral DSA. [Immediately postdose]

   Using the following 5-point scale, the Investigator reviewed the images for motion artifact in vessels distal to the knee: 0 = None; 1 = Mild, not significant; 2 = Significant, but correctable; 3 = Degrades image quality; 4 = Images uninterpretable. Scores of 3 and 4 were counted as significant motion artifacts.

3. The Number of Participants Requiring Repeat Injection(s) Following Intraarterial Administration of ISOVUE-250 or VISIPAQUE 270 in Peripheral DSA. [Immediately postdose]

   The Investigator assessed the images and recorded the number of repeat power injections required due to motion artifacts for each participant.

4. The Number of Participants With Adequate Quality of Opacification Following Intraarterial Administration of ISOVUE-250 or VISIPAQUE 270 in Peripheral DSA [Immediately postdose]

   The Investigator assessed all study images obtained for each patient using a 2-point scale (1 = adequate quality; 2 = inadequate quality); assessment was independent of factors or problems relating to the underlying patient condition or the imaging parameters selected. Results are provided for patients with adequate quality.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• provides written informed consent;

• at least 18 years of age;

• scheduled to undergo peripheral DSA for the diagnosis and/or treatment of PAOD

Exclusion Criteria:

• pregnant or lactating female;

• known allergies to one more more ingredients in wither product;

• history of severe congestive heart failure (Class IV);

• previously enrolled or received an investigational compound within 30 days;

• history of hypersensitivity to iodinated contrast agents;

• renal impairment eGFR <60 mL/min/1.73m2, calculated using the MDRD study equation

• any other medical condition decreasing chances of obtaining reliable data

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bracco Diagnostics	Princeton	New Jersey	United States

Sponsors and Collaborators

• Bracco Diagnostics, Inc

Investigators

• Study Director: Martin Krix, M.D., Bracco Diagnostics, Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bracco Diagnostics, Inc
• ClinicalTrials.gov Identifier: NCT01075217
• Other Study ID Numbers: IOP 119
• First Posted: Feb 25, 2010
• Last Update Posted: May 30, 2013
• Last Verified: Apr 1, 2012

• Keywords provided by Bracco Diagnostics, Inc: Peripheral arterial occlusive disease (PAOD)
• Additional relevant MeSH terms: Arterial Occlusive Diseases; Peripheral Arterial Disease

Study Results

Participant Flow

Recruitment Details	Study start date: April 2010 (first patient received study agent); Study completion date: December 2011 (final collection date for primary outcome measure) This study was conducted in 6 clinical sites across the United States and 1 in Canada.

Arm/Group Title	Isovue 250	Visipaque 270
Arm/Group Description	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).
Period Title: Overall Study
STARTED	84	85
COMPLETED	82	84
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Isovue 250	Visipaque 270	Total
Arm/Group Description	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).	Total of all reporting groups
Overall Participants	84	85	169
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.1 (8.77)	63.1 (8.65)	63.6 (8.70)
Sex: Female, Male (Count of Participants)
Female	30 35.7%	28 32.9%	58 34.3%
Male	54 64.3%	57 67.1%	111 65.7%
Race/Ethnicity, Customized (participants) [Number]
White	68 81%	71 83.5%	139 82.2%
Black or African American	15 17.9%	13 15.3%	28 16.6%
Asian	1 1.2%	0 0%	1 0.6%
Hispanic	0 0%	1 1.2%	1 0.6%

Outcome Measures

1. Primary Outcome

Title	Level of Pain/Heat in the Lower Extremities Scored by the Participants on the Visual Analog Scale (VAS) Following Intra-arterial Administration of ISOVUE-250 or VISIPAQUE 270 in Peripheral DSA
Description	The 10-centimeter Pain VAS was completed by the Group 1 patients to assess his/her pain level (not scoring heat separately from pain) in the lower extremity of interest. The scale was 0 to 10 cm, with the left end (0 cm)of the scale indicating no pain and the right end (10 cm) of the scale indicating the worst pain. The 10-centimeter Pain VAS (excluding Heat assessment, which was separately assessed) was completed by the Group 2 patients to assess his/her pain level in the lower extremity of interest. The scale was 0 to 10 cm, with the left end (0 cm)of the scale indicating no pain and the right end (10 cm) of the scale indicating the worst pain. Group 1 completed the Pain VAS (heat not separate from pain). Group 2 completed the Pain VAS for pain only and, separately, the Heat VAS for heat only.
Time Frame	immediately after administration of agent using a power injector for the administration

Outcome Measure Data

Analysis Population Description

Patients who received study agent, had the corresponding endpoint evaluations available and had no deviations from the planned protocol were included in the analysis.

Arm/Group Title	Isovue 250 VAS Score Prior to Injection (Baseline)	Isovue 250 VAS Score Immediately After Injection	Visipaque 270 VAS Score Prior to Injection (Baseline)	Visipaque 270 VAS Score Immediately After Injection
Arm/Group Description	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).
Measure Participants	77	77	82	82
Group 1 pain and heat not separate (n=42,42,48,48)	0.6 (1.64)	3.1 (3.20)	0.3 (0.87)	0.7 (1.52)
Group 2 pain and heat separate (n=35,35,34,34)	0.4 (1.5)	1.2 (2.10)	0.2 (0.77)	0.8 (1.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Isovue 250 VAS Score Immediately After Injection, Visipaque 270 VAS Score Immediately After Injection
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value provided is for the difference in pain assessment between Isovue and Visipaque in Group 1, i.e., pain was not assessed separately from heat.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; 1.4 to 3.5
	Parameter Dispersion	Type: Standard Deviation; Value: 2.45
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Isovue 250 VAS Score Immediately After Injection, Visipaque 270 VAS Score Immediately After Injection
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3244
	Comments	P-value provided is for the difference in pain assessment between Isovue and Visipaque in Group 2, i.e., pain was assessed separately from heat.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -0.5 to 1.4
	Parameter Dispersion	Type: Standard Deviation; Value: 1.94
	Estimation Comments

2. Secondary Outcome

Title	Level of Heat in the Lower Extremities Scored by Group 2 as Assessed on the Heat VAS Following Intraarterial Administration of ISOVUE-250 or VISIPAQUE 270 in Peripheral DSA
Description	The 10-centimeter Heat VAS was completed by the Group 2 patients to assess his/her heat level (separately from pain) in the lower extremity of interest. The scale was 0 to 10 cm, with the left end (0 cm)of the scale indicating no heat and the right end (10 cm) of the scale indicating the worst heat. The Heat VAS was completed by the patient before completing the Pain VAS to assess pain.
Time Frame	Immediately after administration of agent using a power injector for the administration

Outcome Measure Data

Analysis Population Description

Patients who did not deviate from the planned protocol and had the corresponding endpoint evaluations available were included in the analysis. Group 2 patients provided an assessment of heat by the Heat VAS prior to assessing pain by the Pain VAS.

Arm/Group Title	Isovue 250 VAS Score Immediately After Injection	Visipaque 270 VAS Score Immedicately After Injection
Arm/Group Description	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).
Measure Participants	35	34
Mean (Standard Deviation) [centimeters]	3.3 (2.57)	1.7 (2.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Isovue 250 VAS Score Prior to Injection (Baseline), Isovue 250 VAS Score Immediately After Injection
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0059
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; 0.5 to 2.7
	Parameter Dispersion	Type: Standard Deviation; Value: 2.35
	Estimation Comments

3. Secondary Outcome

Title	The Number of Participants With Significant Motion Artifacts (Scores of 3 or 4) Following Intraarterial Administration of ISOVUE-250 or VISIPAQUE 270 in Peripheral DSA.
Description	Using the following 5-point scale, the Investigator reviewed the images for motion artifact in vessels distal to the knee: 0 = None; 1 = Mild, not significant; 2 = Significant, but correctable; 3 = Degrades image quality; 4 = Images uninterpretable. Scores of 3 and 4 were counted as significant motion artifacts.
Time Frame	Immediately postdose

Outcome Measure Data

Analysis Population Description

Patients who did not deviate from the planned protocol and had the corresponding endpoint evaluations available were included in the analysis. Patients with significant motion artifact were those with a score of 3 or 4 for motion artifacts in vessels distal to the knee

Arm/Group Title	Isovue 250 Immediately After Injection	Visipaque 270 Immediately After Injection
Arm/Group Description	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).
Measure Participants	77	82
Number [participants]	2 2.4%	2 2.4%

4. Secondary Outcome

Title	The Number of Participants Requiring Repeat Injection(s) Following Intraarterial Administration of ISOVUE-250 or VISIPAQUE 270 in Peripheral DSA.
Description	The Investigator assessed the images and recorded the number of repeat power injections required due to motion artifacts for each participant.
Time Frame	Immediately postdose

Outcome Measure Data

Analysis Population Description

Patients who did not deviate from the planned protocol and had the corresponding endpoint evaluations available were included in the analysis.

Arm/Group Title	Isovue 250 Immediately After Injection	Visipaque 270 Immediately After Injection
Arm/Group Description	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).
Measure Participants	77	82
Number [participants]	3 3.6%	1 1.2%

5. Secondary Outcome

Title	The Number of Participants With Adequate Quality of Opacification Following Intraarterial Administration of ISOVUE-250 or VISIPAQUE 270 in Peripheral DSA
Description	The Investigator assessed all study images obtained for each patient using a 2-point scale (1 = adequate quality; 2 = inadequate quality); assessment was independent of factors or problems relating to the underlying patient condition or the imaging parameters selected. Results are provided for patients with adequate quality.
Time Frame	Immediately postdose

Outcome Measure Data

Analysis Population Description

Patients who did not deviate from the planned protocol and had the corresponding endpoint evaluations available were included in the analysis.

Arm/Group Title	Isovue 250 Quality of Opacification After Injection	Visipaque 270 Quality of Opacification After Injection
Arm/Group Description	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).
Measure Participants	77	82
Number [participants]	75 89.3%	82 96.5%

Adverse Events

Time Frame	Start of investigational product administration through the follow-up period of 1 hour post-injection
Arm/Group Title	Isovue 250		Visipaque 270
Arm/Group Description	Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).		Intraarterial injection in one of the following 3 locations: aortic bifurcation (total volume 15-20 mL), iliac arteries (total volume 10-12 mL), or superficial femoral artery (total volume 8-12 mL to view only thigh, 10-15 mL to view calf as well, 20 mL for full runoff to foot).
All Cause Mortality
	Isovue 250		Visipaque 270
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Isovue 250		Visipaque 270
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/84 (1.2%)		1/85 (1.2%)
Vascular disorders
Aortic rupture	1/84 (1.2%)	1	0/85 (0%)	0
Embolism arterial	0/84 (0%)	0	1/85 (1.2%)	1
Peripheral arterial dissection	1/84 (1.2%)	1	0/85 (0%)	0
Other (Not Including Serious) Adverse Events
	Isovue 250		Visipaque 270
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/84 (7.1%)		1/85 (1.2%)
Musculoskeletal and connective tissue disorders
Back pain	6/84 (7.1%)	6	1/85 (1.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. For one site, there is a Clinical Trial Cooperative Research and Development Agreement (CRADA) with a restriction of 180 days after pooled data set is published by the sponsor or 180 after data lock of the complete data.