ABLAVAR® - Clinical Evidence

ABLAVAR^® Clinical Studies¹

Safety and efficacy of ABLAVAR^® were assessed in 2 multicenter, open-label, Phase 3 clinical trials. In both trials, patients with known or suspected peripheral vascular disease underwent MRA with and without ABLAVAR^® as well as catheter-based X-ray arteriography. Diagnostic efficacy was based upon comparisons of sensitivity and specificity between MRA with and without ABLAVAR^®, with X-ray arteriography as the reference standard.

Out of 493 patients enrolled in these 2 trials, 424 were included in the comparison of the diagnostic efficacy of ABLAVAR^®-MRA to that of non-contrast MRA in detection/exclusion of occlusive vascular disease (≥50% stenosis) in 7 vessel-segments in the aortoiliac region. The interpretation of MRA images from both trials was conducted by 3 independent radiologist readers who were blinded to clinical data, including the results of X-ray arteriography. In these 424 patients, the median age was 67 years with a range of 29 to 87 years; 58% of the patients were over 65 years of age; 83% were white and 68% were male.

The primary efficacy analyses were designed to demonstrate superiority in sensitivity and noninferiority in specificity of ABLAVAR^®-MRA as compared to non-contrast MRA at the vessel-segment level. The uninterpretable images were assigned an outcome of “wrong diagnosis.” Additionally, success was also based upon acceptable performance characteristics for the uninterpretable non-contrast MRA vessel segments that became interpretable following ABLAVAR^® administration. Specifically, the sensitivity and specificity for these ABLAVAR^® images were required to exceed 50%. These pre-specified success criteria were to be achieved by at least the same 2 readers for all primary analyses.

Superiority in sensitivity and non-inferiority in specificity was demonstrated for ABLAVAR^®-MRA by all 3 blinded readers. On average, 316 vessel segments were assessed for sensitivity and 2230 for specificity, by each reader. Table 1 summarizes the efficacy results, by reader.

Table 1. Performance Characteristics of ABLAVAR^®-MRA and Non-contrast MRA

Reader	Sensitivity			Specificity
Reader	ABLAVAR^® -MRA [A]	Non-contrast MRA [B]	[A]–[B] (95% CI)^a	ABLAVAR^® -MRA [A]	Non-contrast MRA [B]	[A]–[B] (95% CI)^a
1	89%	69%	20 % (15%, 25%)	72%	71%	1% (-3%, 5%)
2	82%	70%	12% (7%,17%)	81%	73%	8% (4%, 12%)
3	79%	64%	15% (9%, 21%)	85%	85%	0% (-2%, 2%)
^a (Based on cluster-corrected McNemar Test)

Among the 3 readers, 5% to 12% of the vessel-segments were deemed uninterpretable by non-contrast MRA. For these vessel segments, sensitivity of ABLAVAR^® MRA ranged from 72% [95% CI (54%, 90%)] to 97% [95% CI (93%, 100%)], and specificity ranged from 72% [95% CI (67%, 76%)] to 84% [95% CI (81%, 88%)].

References

1. ABLAVAR^® [package insert]. North Billerica, MA: Lantheus Medical Imaging, Inc.; 2011.

INDICATIONS:

ABLAVAR^® is indicated for use as a contrast agent in magnetic resonance angiography (MRA) to evaluate aortoiliac occlusive disease (AIOD) in adults with known or suspected peripheral vascular disease.

CONTRAINDICATIONS:

History of a prior allergic reaction to a gadolinium-based contrast agent.

IMPORTANT SAFETY INFORMATION:

WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF)

Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs.

The risk for NSF appears highest among patients with:

chronic, severe kidney disease (GFR < 30 mL/min/1.73m²), or
acute kidney injury.

Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g. age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing.
For patients at highest risk for NSF, do not exceed the recommended ABLAVAR dose and allow a sufficient period of time for elimination of the drug from the body prior to re-administration.

ABLAVAR^® Injection: As with other contrast media, the possibility of serious or life-threatening anaphylactic or anaphylactoid reactions, including cardiovascular, respiratory and/or cutaneous manifestations, should always be considered. As with other gadolinium based contrast agents, caution should be exercised in patients with renal insufficiency due to the possibility of further deterioration in renal function.

In clinical trials, a small increase (2.8 msec) in the average change from baseline in QTc was observed at 45 minutes following ABLAVAR^® administration. These QTc prolongations were not associated with arrhythmias or symptoms. Caution should be used in patients at high risk for arrhythmias due to baseline QTc prolongation.

Have emergency resuscitative equipment available prior to and during ABLAVAR^® administration.

Please see full Prescribing Information, including boxed WARNING regarding Nephrogenic Systemic Fibrosis (NSF).