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THE
MULTI-ORGAN
SOLUTION
PRESERVATION
AND PROTECTION IN
ORGAN TRANSPLANTATION
LIVER
PANCREAS
KIDNEY
HEART
Please see accompanying Prescribing Information.

Clinical Trials Compared CUSTODIOL <strong>®</strong> (<strong>HTK</strong> Solution) to
University of Wisconsin (UW) Solution in Adult Liver Transplantation 1-3
Liver: Clinically Proven Preservation* ,1,2
CUSTODIOL UW Solution
Patient survival 90% at 3 mo 79% at 3 mo
83% at 12 mo 79% at 12 mo
Primary non-function (PNF) 2.3% 3.9%
Initial poor function (IPF) † 6.5% 6.6%
Primary dysfunction rate (PNF + INF) 8.9% 10.5%
Fair function † 13.1% 6.6%
Good function † 76.6% 82.9%
Rejection episodes 29.2% 32.9%
Liver: Overall Patient Survival 30 Months
After Transplant 2
CUSTODIOL UW Solution
77% 74%
LIVER
TRANSPLANTATION
Greater than 75% survival
rate at 30 months among
patients receiving livers
preserved with CUSTODIOL ‡,3
In the first North American study to compare UW solution and <strong>HTK</strong> solution in general use for liver
transplantation, Mangus et al 4 report no significant differences in clinical outcomes for 1-year graft and
patient survival, primary non-function, and 1-month initial function.
Graft and Patient Survival in Liver Transplantation with UW and <strong>HTK</strong> Preservation
Solutions: 1-, 6-, and 12-Month Outcome Data 4
1 Month 6 Months 12 Months
Graft Survival, %
UW 91.7 86.2 81.7
<strong>HTK</strong>
Patient Survival, %
92.0 85.5 80.8
UW 93.1 87.7 84.6
<strong>HTK</strong> 93.1 86.2 82.1
P = NS for comparison of UW and <strong>HTK</strong> at all time points. Follow-up numbers: 1-month UW n = 204, <strong>HTK</strong> n = 174, Total n = 378;
6-months UW n = 195, <strong>HTK</strong> n = 138, Total n = 333; 12-months UW n = 175, <strong>HTK</strong> n = 78, Total n = 253.
* Multicenter trial comparing results of orthotopic liver transplantations conducted with organs perfused with CUSTODIOL (n=227) and organs perfused
with UW solution (n=79).
† Graft function in first 5 days postimplant was characterized on the basis of blood chemistry as Good (GOT-max 50%);
Fair (GOT 1000-2500 U/L, clotting factor support 2500 U/L, clotting factor support >2 days).
‡ 30-month, prospective, randomized study to compare CUSTODIOL (n=30) and UW solution (n=30) in organ preservation in human liver transplantation.

<strong>HTK</strong> Proves Advantageous in Living Donor Liver Transplantation 5
The safety and efficacy of <strong>HTK</strong> solution were assessed in a prospective study of living donor liver
transplants. In the opinion of authors Ringe et al 5 , <strong>HTK</strong> proved advantageous in comparison to other
preservation solutions because of its low potassium concentration, low viscosity, lack of particles, and
ability to be perfused in situ with no preflushing. <strong>HTK</strong> has improved biliary protection with better
recovery of microcirculatory changes, is ready-to-use, and costs less. The favorable risk-benefit ratio of
<strong>HTK</strong> solution makes it an effective preservation solution for living donor liver transplantation. 5
Organ Preservation Solutions: Major Clinical Differences 5
UW (ViaSpan <strong>®</strong> ) <strong>HTK</strong> (CUSTODIOL <strong>®</strong> )
Composition K + high K + low
Viscosity (1°C) High: 6.2 cP Low: 2.0 cP, ~water
Volume Low: 6–8 L, 50–80 mL/kg High: 10–12 L, 100–175 mL/kg
Flow Lower Higher: x3
Cooling Slower Faster
Additives Several: fresh GSH Ready-to-use
Filters (100 μm No
Flushing Yes No
Adverse events Cardiac arrest None
In situ protection No Heart, kidney, liver
Costs Higher: $1,962–2,616 Lower: $1,500–1,800
cP–centipoise.
Major advantages of <strong>HTK</strong> solution are5 :
• Low potassium concentration • Low viscosity
• No particulate matter • In situ perfusion
• No need to flush before reperfusion • Improved biliary protection
• Better recovery of microcirculatory changes
• Lower costs
• Ready-to-use
Liver Transplantation Editorial: Researchers Compare and Evaluate Solutions
In outcomes data presented to the 2003 American Transplant Congress by University of Pittsburgh
researchers, <strong>HTK</strong> solution exceeded expectations and was found to be as effective as UW solution in
liver transplantation with extended preservation (more than 14 hours of cold ischemia time). 6
A higher rate of late biliary complications in UW-preserved livers (both cadaveric and living donor) has
been reported when compared to <strong>HTK</strong>-preserved organs. 7
In their editorial, Eghtesad, Aucejo, and Fung consider these findings. 8
"Possible explanations for the lower incidence of biliary complications may be attributed to greater
penetration of the <strong>HTK</strong> solution through the small capillary system supplying the bile ducts due to lower
viscosity of the solution, especially at lower temperatures, and/or lack of macroaggregate formation of
adenosine crystals and plastic byproducts in the solution, which may cause occlusion of small capillaries
at the time of perfusion.” 8,9
<strong>®</strong>
ViaSpan is a registered trademark of Barr Laboratories, Inc.
CUSTODIOL is a registered trademark of Dr. Franz Köhler Chemie GmbH,
Alsbach-Hähnlein, Germany.
Please see accompanying Prescribing Information.

Initial Experience Using Histidine-Tryptophan-Ketoglutarate (<strong>HTK</strong>)
Solution in Clinical Pancreas Transplantation 10
• Venous effluent during back-table flushing was clear in the <strong>HTK</strong> group pancreata but initially bloody
in all pancreas grafts in the UW solution group.*
• Graft inflammation/pancreatitis was seen in 5 patients (23%) in the <strong>HTK</strong> group and 4 patients (18%)
in the UW group after reperfusion of the pancreas.*
– Histologic evaluation of <strong>HTK</strong> pancreas allografts before and after reperfusion showed increased
interstitial edema and cellular swelling. The initial edema did not appear to influence the biochemical
function, however, as there was no parenchymal destruction. 10
• The <strong>HTK</strong> solution is devoid of colloid, and its viscosity is similar to water, with a viscosity index of
1.8 cP (vs 5.7 cP for UW) at 5°C. 11
• As the pancreas is a low-flow organ, it will be more readily perfused, cooled, and flushed with
<strong>HTK</strong> solution than with UW solution.
Clinical Outcomes: Survival and Complications 10
Number of Patients <strong>HTK</strong> UW P Value
Number of patients 16 17
Survival, † %
Patient 100 100 NA
Graft 93.8 100 0.49 ‡
Complications, n (%)
Mucus fistula 5 (31.3%) 3 (17.6%) 0.44 ‡
Venous thrombosis 0 0 NA
Sepsis 1 (6.3%) 0 0.49 ‡
† 1 month posttransplantation; ‡ Fisher’s exact test.
PANCREAS
TRANSPLANTATION
*Subjective observation noted during back-table preparation and after pancreas reperfusion. 7

Comparison of <strong>HTK</strong> Solution and UW Solution for Organ Preservation
in Clinical Pancreas Transplantation 12
• In their comparative study, Fridell et al reported no clinically significant differences between UW and
<strong>HTK</strong> solution for perfusion and preservation of pancreas allografts in terms of patient or graft survival
and early graft function.
• Patient and graft survivals at the completion of the follow-up period were 100% for both <strong>HTK</strong> and
UW groups. By time of hospital discharge, all patients had discontinued insulin.
• To date, <strong>HTK</strong> has been found to be a safe solution for pancreas preservation with results comparable
to those of UW solution.
• The outcome for all 10 patients in the <strong>HTK</strong> group was excellent with no delayed graft function or
graft loss.
Clinical Outcomes: Survival 12
<strong>HTK</strong> UW
Number of patients
Survival, %
10 10
Patient 100 100
Graft 100 100
Transplant Characteristics 12
Type <strong>HTK</strong> UW
SPK 8 7
PAK 2 3
SPK–simultaneous pancreas and kidney transplant; PAK–pancreas after kidney transplant.
Other Findings 12
• Both groups had similar serial serum fasting glucose levels with normal glucose values obtained
within the first postoperative day.
• There was a similar curve in both groups in serial amylase levels.
• Both groups showed similar peak serum amylase levels (245±184 U/L for UW and 260±145 U/L for
<strong>HTK</strong>, P=0.85), but the <strong>HTK</strong> group tended to reach this peak later.
• As anticipated, a greater volume of <strong>HTK</strong> solution was used to perfuse the donor organs in situ due
to the lower viscosity of <strong>HTK</strong> solution as compared to UW solution.
• Despite the greater volume of <strong>HTK</strong> solution required,
perfusion remained less costly than with UW solution.
Please see accompanying Prescribing Information.
<strong>®</strong>

Advanced Protection for Graft Survival and Function
3-year Graft Survival 3
CUSTODIOL UW Solution
73% 68%
KIDNEY
TRANSPLANTATION
Greater than 70% graft
survival at 3 years among
kidneys preserved with
CUSTODIOL* ,13
• After comparing performance of <strong>HTK</strong> and UW solutions for cold static storage of kidney allografts,
Agarwal, Murdock, and Fridell concluded that <strong>HTK</strong> solution is not inferior to UW solution with
prolonged cold ischemia times (>24 hours), as other authors had suggested. In fact, they noted, <strong>HTK</strong>
solution may provide better protection for the prevention of delayed graft function than UW solution. 14
Recipient Demographics (Cold Ischemia Time >24 Hours) †,13
Category <strong>HTK</strong> UW P Value
n 31 38
Patient survival, % 100 95
Graft survival, % 97 82
Recent creatinine level 1.35 (0.56) 1.29 (0.34) NS
Age, years 48 (13) 48 (17) NS
Male/female, n 21/10 27/11
Panel reactive antibodies 11 (20) 14 (27) NS
Cold ischemia, hrs 31 (6) 29 (6) 0.13
Warm ischemia, mins 38 (18) 29 (9) 0.01
Primary nonfunction, % 3 6 NS
Delayed graft function, % 16 56

HEART
TRANSPLANTATION
Preserve Hearts Intended for Transplantation
Clinically Proven Preservation vs Celsior <strong>®</strong> * ,15
CUSTODIOL Celsior
(n=24) (n=24)
Perioperative graft failure 8.3% 8.3%
Patient survival at 30 days 91.7% 95.8%
Graft survival at 30 days 88.0% 92.0%
*A prospective, randomized, open clinical trial comparing the myocardial preservation properties of CUSTODIOL and Celsior. Fifty consecutive heart
transplant recipients were randomized to either the CUSTODIOL or the Celsior group. Results above represent the first available 48 patients.
• No unexpected adverse events in clinical studies of heart transplantation 16
• Low potassium content allows direct release into patient’s circulatory system 3
• Buffered with histidine and histidine HCl
– Doubles buffering capacity of transplanted organs, which slows drop of pH 11
– Moderates damaging reductions of pH even at higher storage temperatures 11
• Developed originally as a cardioplegic, † CUSTODIOL has been used in almost 2 million cardiac procedures 2
Efficacy Confirmed in More than 1200 Patients ‡,16
Cold Ischemia Time
Median 194.6 min Primary graft failure

Protect Organs Intended for
Transplantation with CUSTODIOL <strong>®</strong>
IMPORTANT CLINICAL ADVANTAGES
• Only solution approved for use in both abdominal and thoracic cavities
• No unexpected adverse events in clinical studies 16 (e.g., arrhythmia and cardiac arrest)
• Low viscosity important in low-flow organs like the pancreas
• Low potassium content allows direct release into recipient’s circulatory system 3
• Buffered with histidine and histidine HCl
– Doubles buffering capacity in transplanted organs, which moderates drop of pH11 – Protects against edema11 GREATER CONVENIENCE
• Water-like viscosity for easier diffusion and faster cooling time 3
• No flushing required 16
• Convenient storage and package sizes
– 1-year shelf life
– 1 /2-liter bottle
– 1-liter, 2-liter, and 5-liter bags
• Ready-to-use—no need for additives or filters
• Less expensive than UW and Celsior solutions
CONFIDENCE
PRESERVATION
AND PROTECTION
• Developed originally as a cardioplegic,* CUSTODIOL has been used in almost
2 million cardiac procedures in Europe 2
CUSTODIOL is indicated for perfusion and flushing of donor livers, pancreata, kidneys, and hearts prior to
removal from the donor or immediately after removal from the donor. The solution is left in the organ
vasculature during hypothermic storage and transport (not for continuous perfusion) to the recipient.
*Not approved for this use in the United States.
Please see accompanying Prescribing Information.

1/2-liter bottle
(500 mL)
1-liter bag
(1000 mL)
References
1. Pokorny H, Grünberger T, Rockenschaub S, et al. Liver transplantation with
<strong>HTK</strong> perfused organs–a multicenter study. Transplantation. 2002;74:36–37.
Abstract.
2. Data on file, Essential Pharmaceuticals, LLC.
3. Erhard J, Lange R, Scherer R, et al. Comparison of histidine-tryptophanketoglutarate
(<strong>HTK</strong>) solution versus University of Wisconsin (UW) solution
for organ preservation in human liver transplantation. A prospective,
randomized study. Transplant Int. 1994;7:177–181.
4. Mangus RS, Tector AJ, Agarwal A, Vianna R, Murdock P, Fridell JA.
Comparison of histidine-tryptophan-ketoglutarate solution (<strong>HTK</strong>) and
University of Wisconsin solution (UW) in adult liver transplantation.
Liver Transpl. 2006;12:226–230.
5. Ringe B, Braun F, Moritz M, Zeldin G, Soriano H, Meyers W. Safety and
efficacy of living donor liver preservation with <strong>HTK</strong> solution. Transplant Proc.
2005;37:316–319.
6. Eghtesad B, Broznick B, Kusum P, et al. Comparison of histidinetryptophan-ketoglutarate
(<strong>HTK</strong>) solution versus University of Wisconsin
(UW) solution for organ preservation in liver transplantation. Am J Transpl.
2003;3(suppl 5):452. Abstract 1172.
7. Canelo R, Hakim NS, Ringe B. Experience with hystidine tryptophan
ketoglutarate versus University of Wisconsin preservation solutions in
transplantation. Int Surg. 2003;88(3):145-151.
8. Eghtesad B, Aucejo F, Fung JJ. Preservation solutions in liver transplantation:
What are the options? [editorial]. Liver Transpl. 2006;12:196–198.
9. Tullius SG, Filatenkow A, Horch D, et al. Accumulation of crystal deposits
in abdominal organs following perfusion with defrosted University of
Wisconsin solutions. Am J Transplant. 2002;2(7):627-630.
10. Potdar S, Malek S, Eghtesad B, et al. Initial experience using histidinetryptophan-ketoglutarate
solution in clinical pancreas transplantation.
Clin Transplant. 2004;18:661–665.
11. Gebhard MM, Kirlum HJ, Schlegel C. Organ preservation with the solution
<strong>HTK</strong>. In: Hesse UJ, de Hemptinne B, eds. Organ Preservation with <strong>HTK</strong> and
UW Solution: Update on Clinical Use and Experimental Studies. Lengerich,
Germany: Pabst Science Publishers; 1999:75-87.
2-liter bag
(2000 mL)
5-liter bag
(5000 mL)
12. Fridell JA, Agarwal A, Milgrom ML, Goggins WC, Murdock P, Pescovitz MD.
Comparison of histidine-tryptophan-ketoglutarate solution and University of
Wisconsin solution for organ preservation in clinical pancreas transplantation.
Transplantation. 2004;77(8):1304–1306.
13. de Boer J, De Meester J, Smits JMA, et al. Eurotransplant randomized
multicenter kidney graft preservation study comparing <strong>HTK</strong> with UW and
Euro-Collins. Transplant Int. 1999;12:447-453.
14. Agarwal A, Murdock P, Fridell JA. Comparison of histidine-tryptophan
ketoglutarate solution and University of Wisconsin solution in prolonged
cold preservation of kidney allografts. Transplantation. 2006;81(3):1–3.
15. Wieselthaler GM, Chevtchik O, Konetschny R, et al. Improved graft function
using a new myocardial preservation solution: Celsior. Preliminary data from
a randomized prospective study. Transplant Proc. 1999;31:2067-2068.
16. CUSTODIOL [package insert]. Newtown, PA: Essential Pharmaceuticals, LLC;
2006.
17. Ackemann J, Gross W, Mory M, Schaefer M, Gebhard, MM. Celsior versus
<strong>Custodiol</strong>: Early postischemic recovery after cardioplegia and ischemia at 5°C.
Ann Thorac Surg. 2002;74:522–529.