Coronary Artery DiseasePhase 2NCT01681095

Custodiol-HTK (Histidine-tryptophan-ketoglutarate) Solution as a Cardioplegic Agent

A Phase 2 study testing Custodiol HTK and Cold Blood Cardioplegia in people with Coronary Artery Disease and Myocardial Ischemia, run by Marc Sakwa, MD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of the study is to demonstrate that Custodiol-HTK is not inferior to cold cardioplegic solution in patients undergoing cardiovascular surgery requiring cardioplegic arrest. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Coronary Artery Disease, Myocardial Ischemia, Coronary Disease
What is being tested?: Custodiol HTK and Cold Blood Cardioplegia
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 110 participants
Where: 1 siteUnited States
Study dates: Aug 2012to Apr 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients undergoing scheduled cardiac surgery requiring cardioplegic arrest with expected cross clamp time>45 minutes
Patients age 18 and older

Who cannot join

Pregnant women*
Urgent or emergent cases
Repeat cardiovascular surgical procedures
Patients on dialysis
Any known allergies to components of either cardioplegia solution *All women of child bearing potential must have a negative serum or urine pregnancy test.

Trial locations and contacts

1 site in 1 country.

United States1 site

William Beaumont Hospital
Royal Oak, Michigan, 48073

Other trials in United States

About this study

Official title: Custodiol-HTK Solution as a Cardioplegic Agent- A Prospective Non-Inferiority Randomized Clinical Trial

The purpose of the study is to demonstrate that Custodiol-HTK is not inferior to cold cardioplegic solution in patients undergoing cardiovascular surgery requiring cardioplegic arrest.

Read the detailed description

The objective of this study is to demonstrate that Custodiol is not inferior to cold cardioplegic solution for myocardial protection by comparing standard cold blood cardioplegia to Custodiol solution with respect to myocardial injury as measured by Creatine phosphokinase MB isoenzyme (CK-MB),troponin-I at 7 hours post surgery and changes in ejection fraction by trans-thoracic echocardiogram (TTE)or trans-esophageal echocardiogram (TEE) at 24 hours post surgery.

Conditions: Coronary Artery Disease, Myocardial Ischemia, Coronary Disease, Heart Diseases, Valvular Heart Disease
Being tested: Custodiol HTK, Cold Blood Cardioplegia
Keywords: Physiological Effects of Drugs, Cardiovascular Agents, Therapeutic Uses, Pharmacologic Actions, Mannitol, Cardiac Surgery, Cardioplegic Solutions, HTK solution, Myocardial protection, Coronary Artery Disease, Myocardial Ischemia, Coronary Disease, Heart Diseases
Medical subject headings: Coronary Artery Disease, Myocardial Ischemia, Coronary Disease, Heart Diseases, Heart Valve Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Custodiol HTKDrug
Also called Histidine-tryptophan-ketoglutarate cardioplegia solution
After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 10°C.
Cold Blood CardioplegiaDrug
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional > 200 mL was administered in an antegrade/retrograde fashion throughout the remainder of the case. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.

Study groups in NCT01681095
Study group	Role	What they receive
Cardioplegia: Custodiol HTK Solution	Experimental	Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C. Receives: Drug: Custodiol HTK
Cold Blood Cardioplegia	Active comparator	Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional > 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C. Receives: Drug: Cold Blood Cardioplegia

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Creatine Phosphokinase-MB Isoenzyme (CK-MB)
Creatine phosphokinase MB isoenzyme (CK-MB) difference from baseline 7 hours post surgery
Measured: Baseline and 7 hours post surgery
Change in Troponin I
Troponin I values, difference from baseline 7 hours post surgery
Measured: Baseline and 7 hours post surgery
Changes in Left Ventricular (LV) Ejection Fraction (EF) by Transthoracic Echocardiogram (TTE)
LV ejection fraction by TTE, difference from baseline at 24 hours post surgery
Measured: Baseline and 24 hours post surgery

Secondary outcomes (14)

Cardiac Dysrhythmias
Number of participants with new or worsening of cardiac dysrhythmias
Measured: up to 36 hrs post surgery
All Cause Mortality
Number of participants with all-cause mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative
Measured: 30 days post procedure
Cardiovascular Mortality
Number of participants with cardiovascular-related mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative
Measured: 30 days post procedure
Time on Mechanically Assisted Ventilation
time in hours from intubation to extubation, with intervening transport to the cardiac critical care unit.
Measured: up to 36 hours post procedure
Duration of Vasopressor / Inotropic Agent
Total time in minutes on any vasopressor or inotropic agent, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine
Measured: up to 36 hours post procedure
Postoperative Inotropic Infusion >20 Minutes
Number of patients receiving vasopressor or inotropic infusion for greater than 20 minutes in the operating room, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine.
Measured: during operative procedure
Intensive Care Unit (ICU) Length of Stay
Duration of stay in ICU, from ICU admission to ICU discharge
Measured: up to 100 days after admission
Myocardial Infarction
Number or participants fulfilling at least two of the following 3 criteria: (1) CK-MB of 100 ug/L or more and/or troponin-I of 3.0 ug/L or more, (2) appearance of new postoperative Q waves on the EKG of more than 0.03 seconds, and (3) a new hypokinetic or akinetic area in the left or right ventricle by echocardiography.
Measured: up to 36 hours post procedure
Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)
CK-MB measured pre-operatively
Measured: pre-operative
Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)
CK-MB measured 24 hours post-operatively
Measured: 24 hours post procedure
Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)
CK-MB measured 48 hours post-operatively
Measured: 48 hours post procedure
Cardiac Marker - Troponin-I
Troponin-I measured pre-operatively
Measured: pre-operatively
Cardiac Marker - Troponin-I
Troponin-I measured 24 hours post-operative
Measured: 24 hours post procedure
Cardiac Marker - Troponin-I
Troponin-I measured 48 hours post-operative
Measured: 48 hours post procedure

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2012Apr 2016

First posted7 Sep 2012 (estimated)
Study startAug 2012
Primary completionAug 2014
Study completionApr 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (21)Papers the sponsor has linked to this study.
Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 110 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01681095
Sponsor's protocol ID: 2012-125
Status last verified: Jan 2017
First submitted: 10 Aug 2012
Last updated: 6 Aug 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Braathen B, Jeppsson A, Schersten H, Hagen OM, Vengen O, Rexius H, Lepore V, Tonnessen T. One single dose of histidine-tryptophan-ketoglutarate solution gives equally good myocardial protection in elective mitral valve surgery as repetitive cold blood cardioplegia: a prospective randomized study. J Thorac Cardiovasc Surg. 2011 Apr;141(4):995-1001. doi: 10.1016/j.jtcvs.2010.07.011. Epub 2010 Aug 30.
PubMed 20800244
Careaga G, Salazar D, Tellez S, Sanchez O, Borrayo G, Arguero R. Clinical impact of histidine-ketoglutarate-tryptophan (HTK) cardioplegic solution on the perioperative period in open heart surgery patients. Arch Med Res. 2001 Jul-Aug;32(4):296-9. doi: 10.1016/s0188-4409(01)00296-x.
PubMed 11440787
Hachida M, Ookado A, Nonoyama M, Koyanagi H. Effect of HTK solution for myocardial preservation. J Cardiovasc Surg (Torino). 1996 Jun;37(3):269-74.
PubMed 8698763
Yang Q, He GW. Effect of cardioplegic and organ preservation solutions and their components on coronary endothelium-derived relaxing factors. Ann Thorac Surg. 2005 Aug;80(2):757-67. doi: 10.1016/j.athoracsur.2004.10.003.
PubMed 16039259
Beyersdorf F, Krause E, Sarai K, Sieber B, Deutschlander N, Zimmer G, Mainka L, Probst S, Zegelman M, Schneider W, et al. Clinical evaluation of hypothermic ventricular fibrillation, multi-dose blood cardioplegia, and single-dose Bretschneider cardioplegia in coronary surgery. Thorac Cardiovasc Surg. 1990 Feb;38(1):20-9. doi: 10.1055/s-2007-1013985.
PubMed 2106735
Savini C, Camurri N, Castelli A, Dell'Amore A, Pacini D, Suarez SM, Grillone G, Di Bartolomeo R. Myocardial protection using HTK solution in minimally invasive mitral valve surgery. Heart Surg Forum. 2005;8(1):E25-7. doi: 10.1532/HSF98.20041145.
PubMed 15769709
Braathen B, Tonnessen T. Cold blood cardioplegia reduces the increase in cardiac enzyme levels compared with cold crystalloid cardioplegia in patients undergoing aortic valve replacement for isolated aortic stenosis. J Thorac Cardiovasc Surg. 2010 Apr;139(4):874-80. doi: 10.1016/j.jtcvs.2009.05.036. Epub 2009 Jul 26.
PubMed 19660338
Hendrikx M, Jiang H, Gutermann H, Toelsie J, Renard D, Briers A, Pauwels JL, Mees U. Release of cardiac troponin I in antegrade crystalloid versus cold blood cardioplegia. J Thorac Cardiovasc Surg. 1999 Sep;118(3):452-9. doi: 10.1016/s0022-5223(99)70182-0.
PubMed 10469959
Aarsaether E, Stenberg TA, Jakobsen O, Busund R. Mechanoenergetic function and troponin T release following cardioplegic arrest induced by St Thomas' and histidine-tryptophan-ketoglutarate cardioplegia--an experimental comparative study in pigs. Interact Cardiovasc Thorac Surg. 2009 Oct;9(4):635-9. doi: 10.1510/icvts.2009.208231. Epub 2009 Jul 23.
PubMed 19628529
Gallandat Huet RC, Karliczek GF, van der Heide JN, Brenken U, Mooi B, van der Broeke JJ, Jenkins I, de Geus AF. Clinical effect of Bretschneider-HTK and St. Thomas cardioplegia on hemodynamic performance after bypass measured using an automatic datalogging database system. Thorac Cardiovasc Surg. 1988 Jun;36(3):151-6. doi: 10.1055/s-2007-1020064.
PubMed 3145585
Arslan A, Sezgin A, Gultekin B, Ozkan S, Akay T, Uguz E, Tasdelen A, Aslamaci S. Low-dose histidine-tryptophan-ketoglutarate solution for myocardial protection. Transplant Proc. 2005 Sep;37(7):3219-22. doi: 10.1016/j.transproceed.2005.08.020.
PubMed 16213352
Fannelop T, Dahle GO, Salminen PR, Moen CA, Matre K, Mongstad A, Eliassen F, Segadal L, Grong K. Multidose cold oxygenated blood is superior to a single dose of Bretschneider HTK-cardioplegia in the pig. Ann Thorac Surg. 2009 Apr;87(4):1205-13. doi: 10.1016/j.athoracsur.2009.01.041.
PubMed 19324152
Schaper J, Scheld HH, Schmidt U, Hehrlein F. Ultrastructural study comparing the efficacy of five different methods of intraoperative myocardial protection in the human heart. J Thorac Cardiovasc Surg. 1986 Jul;92(1):47-55.
PubMed 3088335
Athanasuleas C., Buckberg G. Myocardial protection and cardioplegia. Cardiopulmonary Bypass. New York: CambridgeUniversity Press; 2009: p. 82.
Bical OM, Fromes Y, Paumier D, Gaillard D, Foiret JC, Trivin F. Does warm antegrade intermittent blood cardioplegia really protect the heart during coronary surgery? Cardiovasc Surg. 2001 Apr;9(2):188-93. doi: 10.1177/096721090100900219.
PubMed 11250190

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 6 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Custodiol-HTK Solution as a Cardioplegic Agent- A Prospective Non-Inferiority Randomized Clinical Trial
ClinicalTrials.gov ID: NCT01681095
Acronym / sponsor ID: 2012-125
Conditions: Coronary Artery Disease, Myocardial Ischemia, Coronary Disease, Heart Diseases, Valvular Heart Disease
Keywords: Physiological Effects of Drugs, Cardiovascular Agents, Therapeutic Uses, Pharmacologic Actions, Mannitol, Cardiac Surgery, Cardioplegic Solutions, HTK solution
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 110 participants (actual)
Lead sponsor: Marc Sakwa, MDUniversity, hospital or other
Collaborators: Essential Pharmaceuticals, LLC
Study start: Aug 2012
Primary completion: Aug 2014 (actual)
Study completion: Apr 2016 (actual)
First posted: 7 Sep 2012 (estimated)
Results: Posted 1 Mar 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of the study is to demonstrate that Custodiol-HTK is not inferior to cold cardioplegic solution in patients undergoing cardiovascular surgery requiring cardioplegic arrest.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Cardioplegia: Custodiol HTK Solution	Experimental	Drug: Custodiol HTKCustodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.
Cold Blood Cardioplegia	Active comparator	Drug: Cold Blood CardioplegiaCold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional > 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Patients undergoing scheduled cardiac surgery requiring cardioplegic arrest with expected cross clamp time>45 minutes
Patients age 18 and older

Key exclusion criteria (5 listed)

Pregnant women*
Urgent or emergent cases
Repeat cardiovascular surgical procedures
Patients on dialysis
Any known allergies to components of either cardioplegia solution *All women of child bearing potential must have a negative serum or urine pregnancy test.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Custodiol HTKAlso: Histidine-tryptophan-ketoglutarate cardioplegia solutionAfter cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 10°C.	Drug	Cardioplegia: Custodiol HTK Solution
Cold Blood CardioplegiaAfter cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional > 200 mL was administered in an antegrade/retrograde fashion throughout the remainder of the case. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.	Drug	Cold Blood Cardioplegia

Primary outcome

Change in Creatine Phosphokinase-MB Isoenzyme (CK-MB)
Time frame: Baseline and 7 hours post surgery
Creatine phosphokinase MB isoenzyme (CK-MB) difference from baseline 7 hours post surgery
Change in Troponin I
Time frame: Baseline and 7 hours post surgery
Troponin I values, difference from baseline 7 hours post surgery
Changes in Left Ventricular (LV) Ejection Fraction (EF) by Transthoracic Echocardiogram (TTE)
Time frame: Baseline and 24 hours post surgery
LV ejection fraction by TTE, difference from baseline at 24 hours post surgery

14 secondary outcomes

Cardiac Dysrhythmias
Time frame: up to 36 hrs post surgery
All Cause Mortality
Time frame: 30 days post procedure
Cardiovascular Mortality
Time frame: 30 days post procedure
Time on Mechanically Assisted Ventilation
Time frame: up to 36 hours post procedure
Duration of Vasopressor / Inotropic Agent
Time frame: up to 36 hours post procedure
Postoperative Inotropic Infusion >20 Minutes
Time frame: during operative procedure
Intensive Care Unit (ICU) Length of Stay
Time frame: up to 100 days after admission
Myocardial Infarction
Time frame: up to 36 hours post procedure
Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)
Time frame: pre-operative
Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)
Time frame: 24 hours post procedure
Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)
Time frame: 48 hours post procedure
Cardiac Marker - Troponin-I
Time frame: pre-operatively
Cardiac Marker - Troponin-I
Time frame: 24 hours post procedure
Cardiac Marker - Troponin-I
Time frame: 48 hours post procedure

Results and safety

Results posted to the registry on 1 Mar 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cardioplegia: Custodiol HTK Solution	55	55
Cold Blood Cardioplegia	55	55

Primary outcome: Change in Creatine Phosphokinase-MB Isoenzyme (CK-MB)

Time frame: Baseline and 7 hours post surgery. Median (Inter-Quartile Range). Unit: ng/mL

Measure	Cardioplegia: Custodiol HTK Solution n = 40	Cold Blood Cardioplegia n = 38
Value	18.8 (12.5 to 24)	22.2 (15 to 51)

Population analysed: Patients for which both baseline and 7 hours post surgery values were available

Primary outcome: Change in Troponin I

Time frame: Baseline and 7 hours post surgery. Median (Inter-Quartile Range). Unit: ng/mL

Measure	Cardioplegia: Custodiol HTK Solution n = 55	Cold Blood Cardioplegia n = 55
Value	9.65 (5.47 to 16.00)	10.15 (6.04 to 19.97)

Primary outcome: Changes in Left Ventricular (LV) Ejection Fraction (EF) by Transthoracic Echocardiogram (TTE)

Time frame: Baseline and 24 hours post surgery. Mean (Standard Deviation). Unit: % LV volume

Measure	Cardioplegia: Custodiol HTK Solution n = 51	Cold Blood Cardioplegia n = 51
Value	-0.06 (11)	1.9 (10)

Population analysed: patients for whom both preoperative and 24 hour LV ejection fractions were obtained

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs were evaluated from time of consent to 4 days after surgery.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cardioplegia: Custodiol HTK Solution	3 of 55 (5.5%)	25 of 55 (45.5%)	Not reported
Cold Blood Cardioplegia	9 of 55 (16.4%)	34 of 55 (61.8%)	Not reported

Limitations and caveats (from the sponsor): Adverse events (not serious adverse events) are listed only for events occurring with greater than 5% frequency in at least one of the groups.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 20800244Braathen B, Jeppsson A, Schersten H, Hagen OM, Vengen O, Rexius H, Lepore V, Tonnessen T. One single dose of histidine-tryptophan-ketoglutarate solution gives equally good myocardial protection in elective mitral valve surgery as repetitive cold blood cardioplegia: a prospective randomized study. J Thorac Cardiovasc Surg. 2011 Apr;141(4):995-1001. doi: 10.1016/j.jtcvs.2010.07.011. Epub 2010 Aug 30.
Background: PubMed 11440787Careaga G, Salazar D, Tellez S, Sanchez O, Borrayo G, Arguero R. Clinical impact of histidine-ketoglutarate-tryptophan (HTK) cardioplegic solution on the perioperative period in open heart surgery patients. Arch Med Res. 2001 Jul-Aug;32(4):296-9. doi: 10.1016/s0188-4409(01)00296-x.
Background: PubMed 8698763Hachida M, Ookado A, Nonoyama M, Koyanagi H. Effect of HTK solution for myocardial preservation. J Cardiovasc Surg (Torino). 1996 Jun;37(3):269-74.
Background: PubMed 16039259Yang Q, He GW. Effect of cardioplegic and organ preservation solutions and their components on coronary endothelium-derived relaxing factors. Ann Thorac Surg. 2005 Aug;80(2):757-67. doi: 10.1016/j.athoracsur.2004.10.003.
Background: PubMed 2106735Beyersdorf F, Krause E, Sarai K, Sieber B, Deutschlander N, Zimmer G, Mainka L, Probst S, Zegelman M, Schneider W, et al. Clinical evaluation of hypothermic ventricular fibrillation, multi-dose blood cardioplegia, and single-dose Bretschneider cardioplegia in coronary surgery. Thorac Cardiovasc Surg. 1990 Feb;38(1):20-9. doi: 10.1055/s-2007-1013985.
Background: PubMed 15769709Savini C, Camurri N, Castelli A, Dell'Amore A, Pacini D, Suarez SM, Grillone G, Di Bartolomeo R. Myocardial protection using HTK solution in minimally invasive mitral valve surgery. Heart Surg Forum. 2005;8(1):E25-7. doi: 10.1532/HSF98.20041145.
Background: PubMed 19660338Braathen B, Tonnessen T. Cold blood cardioplegia reduces the increase in cardiac enzyme levels compared with cold crystalloid cardioplegia in patients undergoing aortic valve replacement for isolated aortic stenosis. J Thorac Cardiovasc Surg. 2010 Apr;139(4):874-80. doi: 10.1016/j.jtcvs.2009.05.036. Epub 2009 Jul 26.
Background: PubMed 10469959Hendrikx M, Jiang H, Gutermann H, Toelsie J, Renard D, Briers A, Pauwels JL, Mees U. Release of cardiac troponin I in antegrade crystalloid versus cold blood cardioplegia. J Thorac Cardiovasc Surg. 1999 Sep;118(3):452-9. doi: 10.1016/s0022-5223(99)70182-0.
Background: PubMed 19628529Aarsaether E, Stenberg TA, Jakobsen O, Busund R. Mechanoenergetic function and troponin T release following cardioplegic arrest induced by St Thomas' and histidine-tryptophan-ketoglutarate cardioplegia--an experimental comparative study in pigs. Interact Cardiovasc Thorac Surg. 2009 Oct;9(4):635-9. doi: 10.1510/icvts.2009.208231. Epub 2009 Jul 23.
Background: PubMed 3145585Gallandat Huet RC, Karliczek GF, van der Heide JN, Brenken U, Mooi B, van der Broeke JJ, Jenkins I, de Geus AF. Clinical effect of Bretschneider-HTK and St. Thomas cardioplegia on hemodynamic performance after bypass measured using an automatic datalogging database system. Thorac Cardiovasc Surg. 1988 Jun;36(3):151-6. doi: 10.1055/s-2007-1020064.
Background: PubMed 16213352Arslan A, Sezgin A, Gultekin B, Ozkan S, Akay T, Uguz E, Tasdelen A, Aslamaci S. Low-dose histidine-tryptophan-ketoglutarate solution for myocardial protection. Transplant Proc. 2005 Sep;37(7):3219-22. doi: 10.1016/j.transproceed.2005.08.020.
Background: PubMed 19324152Fannelop T, Dahle GO, Salminen PR, Moen CA, Matre K, Mongstad A, Eliassen F, Segadal L, Grong K. Multidose cold oxygenated blood is superior to a single dose of Bretschneider HTK-cardioplegia in the pig. Ann Thorac Surg. 2009 Apr;87(4):1205-13. doi: 10.1016/j.athoracsur.2009.01.041.
Individual participant dataSharing planned: No

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Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
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The OCTOBER Trial - European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction (OCTOBER)
Ischaemic Heart Disease, Ischemic Heart Disease

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Marc Sakwa, M.D. principal investigator

Beaumont Health

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Custodiol HTK and Cold Blood Cardioplegia in people with Coronary Artery Disease and Myocardial Ischemia, run by Marc Sakwa, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Creatine Phosphokinase-MB Isoenzyme (CK-MB) (time frame: Baseline and 7 hours post surgery). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01681095, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2019.