Download CARE - Clinical Trial Results

CARE
Cardiac Angiography in REnally impaired patients:
A comparison between Iodixanol (Visipaque) and
Iopamidol (Isovue) in high risk patients for
contrast induced nephropathy
CARE
Largest prospective randomized comparison trial of lowosmolar vs iso-osmolar CM.
High risk patients
1.
2.
1.
2.
eGFR <60 ml/min
Cardiac catheterization
Complimentary preventative strategies
3.
1.
2.
Volume expansion with bicarbonate (all centers)
Double dose NAC (some centers)
Rigorous statistical approach
4.
1.
2.
3.
4.
5.
Multiple definitions of CIN
Prospective randomized double blind design
Single laboratory performing serum creatinine analysis
Analysis by time post CM of follow-up serum creatinine
Prospectively defined subgroups – diabetes, NAC
CARE
25 Centers in North America

Inclusion criteria
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
Age >18 years
Documented eGFR >20 and <60
ml/min/1.73m2 from a SCr obtained
w/i 72 h of enrollment
Scheduled for cardiac angiography
Willing to receive periprocedure
prophylaxis per protocol
IV sodium bicarbonate
NAC (by center)

Exclusion criteria






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Pregnant or lactating female
Hx of sensitivity to I-dye
NYHA IV CHF
Hyperthroidism
Unstable renal function or on
dialysis
Contrast dye w/i 7 days prior to
72 h post
Loop diuretics w/i 24 h pre or
post CM administration
Receiving NSAIDs,
aminoglycosides, or other renally
toxic medications
Planned used of adenosine or
dipyridamole during angiography
CARE-Clinical and Procedural Characteristics
of Study Patients
Characteristic
Iopamidol (204)
Iodixanol (210)
P value
72.9 ± 9.0
70.5 ± 9.9
0.04
68/32
60/40
0.15
Weight (kg)
82.7 ±17.7
86.7 ± 20.6
0.03
SCrt (mg/dl)
1.46 ± 0.36
1.44 ± 0.41
0.64
eGFR* (ml/min/1.73m2)
49.3 ±11.6
50.2 ±13.0
0.45
Diabetes (%)
38.2
43.8
0.27
PCI (%)
39.7
39.0
0.92
133.7 ±74.4
136.4 ±71.6
0.70
Age (yr)
Gender M/F (%)
Volume of CM (ml)
Time of post CM SCr (h)
45-71 hours (%)
72-96 hours (%)
>96 hours (%)
t
SCr at baseline
0.94
83.3%
13.2%
3.5%
83.3%
13.8%
2.9%
* By abbreviated MDRD formula
Results: Total Group
n=414
Definition
of CIN
Iopamidol
(n=204)
Iodixanol
(n=210)
95% CI of
difference
(Iop-Iod)
P-value
≥0.5 mg/dl
 SCr
4.4%
6.7%
-6.7, 2.1
0.39
≥25% 
SCr
9.8%
12.4%
-8.6, 3.5
0.44
≥ 25% 
eGFR
5.9%
10.0%
-9.3, 1.1
0.15
Results: Diabetes SubGroup
n=170
Definition
of CIN
Iopamidol
(n=78)
Iodixanol
(n=92)
95% CI of
difference
(Iop – Iod)
P-value
≥0.5 mg/dl
 SCr
5.1%
13.0%
-16.4, 0.5
0.39
≥25% 
SCr
10.3%
15.2%
-14.9, 5.0
0.44
≥ 25% 
eGFR
6.4%
13.0%
-15.4, 2.1
0.15
Results: PCI
n=163
Definition of CIN Iopamidol Iodixanol P value
(81)
(82)
≥ 0.5 mg/dl SCr
2.5%
7.3%
0.28
≥ 25%SCr
4.9%
14.6%
0.06
≥ 25% eGFR
1.2%
12.2%
0.01
Results: NAC
n=168
Definition of CIN Iopamidol Iodixanol P value
(79)
(89)
≥ 0.5 mg/dl SCr
1.3%
6.7%
0.12
≥ 25%SCr
11.4%
12.4%
1.0
≥ 25% eGFR
5.1%
9.0%
0.38
Results
Mean change in peak SCr
Group
Iopamidol
Iodixanol
P value
Total (n=414)
0.07 ± 0.22
0.12 ± 0.23
0.03
Diabetes (n=170)
0.07 ± 0.26
0.16 ± 0.27
0.01
NAC (n=168)
0.05 ± 0.20
0.10 ± 0.22
0.19
CARE Conclusion

There was no difference in the incidence of
CIN between iopamidol (low osmolar CM) and
iodixanol (iso-osmolar CM).
No difference in total group with CKD
 No difference in those with both diabetes and CKD
 No difference in those who underwent PCI
 No difference in those who received NAC

CARE Conclusion

Iopamidol was associated with a significantly
smaller mean increase in serum creatinine
compared to iodixanol.
For total group
 For those with diabetes

CARE-Implications
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Osmolality alone is not the sole determinant of CIN.
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Iopamidol osmolality is 796
Iodixanol osmolality is 290
Prior studies suggesting less CIN with iso-osmolal CM
may be the result of comparisons:

CM agents having different renal toxicity.
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NEPHRIC: comparator=iohexol
RECOVER: comparator=ioxaglate
Different patient populations
Different definitions of renal insufficiency and CIN.
CARE – Comparison with other prospective randomized trials
Low osmolal
(osmolality)
Iso-osmolal
(osmolality)
Condition
Statistical result
Iohexol (844)
Iodixanol (290)
Coronary, CKD (SCr*
3.1), 35% DM
No difference1
Iohexol (844)
Iodixanol (290)
Coronary, CKD (SCr
1.5), 100% DM
Iodixanol superior to
iohexol2
Ioversol (792)
Iodixanol (290)
Coronary, CKD (SCr
2.0), 52% DM
No difference3
Iopamidol (796)
Iodixanol (290)
MDCT, CKD (SCr 1.6)
No difference4
Iopamidol (796)
Iodixanol (290)
Coronary, CKD (SCr
1.45), 41% DM
No difference5
Ioxaglate (600)
Iodixanol (290)
Coronary, CKD (SCr
1.34, 48% DM
Iodixanol superior to
ioxaglate6
*SCr: serum creatinine (mg/dl)
1Chalmer
and Jackson, BJR 1999
2Aspelin et al (NEPHRIC), NEJM 2003
3Rudnick et al, (VALOR), ASN 2005
4Barrett
et al (IMPACT), Invest Rad 2006
5Solomon et al (CARE), TCT 2006
6Jo et al (RECOVER), JACC 2006
Acknowledgements
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CARE was sponsored by Bracco Diagnostics, Inc
CARE investigators:
R. Applegate – Winston Salem, NC
B. Barrett - St. Johns, NL
J.B. Cavender – Birmingham, AL
S. Doucet – Montreal, QC
J. Ducas – Winnipeg, MT
J.T. Eagan – Birmingham, AL
T. Fischell – Kalamazoo, MI
J. Gelormini – Buffalo, NY
R. Katholi – Springfield, IL
R. Kipperman – Oklahoma City, OK
M. Labinaz – Ottawa, ON
J.R. Laird – Washington, DC
E. Mahmud – San Diego, CA
R.G. McKay – Hartford, CT
A.E. Moreyra – New Brunswick, NJ
M. K. Natarajan – Hamilton, ON
K. Niazi – Atlanta, GA
J.S. Reiner – Washington, DC
E. Rivera – Amarillo, TX
S.K. Sharma – New York, NY
R.J. Solomon – Burlington, VT
C.S. Staniloae – New York, NY
M.E. Stillabower – Newark, DE
C. Walker – Houma, LA
I.R. Weinstein – Orlando, FL