Congenital Heart DiseasePhase 2NCT02618824
Role of Terminal Warm Blood Cardioplegia as Myocardial Protection in the Use of Histidine-Tryptophan-Ketoglutarate Cardioplegia in Complex Congenital Heart Surgery
A Phase 2 study testing Histidine Tryptophan Ketoglutarate Solution and Terminal Warm Blood Cardioplegia in people with Congenital Heart Disease, run by National Cardiovascular Center Harapan Kita Hospital Indonesia at 1 site in Indonesia.
Trial summary
Terminal warm blood cardioplegia (TWBC) has been shown to enhance myocardial protection in adult patients. Even in pediatric patients, the use of cold blood cardioplegia followed by administration of TWBC will provide cardioprotective effect similar to adult patients. Read more about this study
- Who is it for?
- Ages Up to 5 years
- Conditions the study is for
- Congenital Heart Disease
- What is being tested?
- Histidine Tryptophan Ketoglutarate Solution and Terminal Warm Blood Cardioplegia
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteIndonesia
- Study dates
- Dec 2015to Dec 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 Up to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patient diagnosed with complex cyanotic congenital heart disease who scheduled for pediatric cardiac surgery
- Aristotle score is 8 and above
- Parents of patient have written informed consent and agree to follow the research procedures
Who cannot join
- Patient diagnosed with an other congenital defect
- Patient diagnosed with rare congenital heart defect and high mortality rate (such as hypoplastic left heart syndrome)
Trial locations and contacts
1 site in 1 country.
Indonesia1 site, 1 recruiting
- Recruiting
National Cardiac Centre Harapan Kita Hospital
Jakarta, Jakarta Special Capital Region, 11420
Pribadi W Busro, MD
About this study
Terminal warm blood cardioplegia (TWBC) has been shown to enhance myocardial protection in adult patients. Even in pediatric patients, the use of cold blood cardioplegia followed by administration of TWBC will provide cardioprotective effect similar to adult patients. Histidine-tryptophan-ketoglutarate (HTK), is attractive for cardiac surgeons because it is administered as a single dose and is claimed to offer myocardial protection for a period of up to 180 minutes allowing performance of complex procedures without interruption. Merging the use of TWBC on the use of HTK cardioplegia, especially for pediatric cardiac cases, have not been investigated. This technique is expected to provide a longer ischemic time and a protective effect against reperfusion injury.
Read the detailed description
The design of this study is a randomized controlled trial in children younger than 5 years old undergoing heart surgery with cardiopulmonary bypass. The objective of this study is to assess the role of TWBC in use of HTK cardioplegia compared with the use of HTK cardioplegia alone in open heart surgery of complex congenital heart disease. This study will be conducted at the National Cardiac Centre Harapan Kita Hospital Indonesia. Surgery will be performed in the operating room of Pediatric and Congenital Cardiac Surgery Unit. This study uses non-probability consecutive sampling. The samples are all pediatric patients with complex congenital heart disease who meet the inclusion criteria and not excluded by the exclusion criteria. Patients will be divided into two groups, the treatment group who received HTK cardioplegia and TWBC, and the control group that only received HTK cardioplegia alone. Hearts will be arrested with HTK solution during cardiac operation. HTK cardioplegia will be given through the aortic root at a dose of 50-60 ml/kg after aortic cross-clamped. For the treatment group, TWBC will be given shortly before the aortic cross clamp is removed at a dose of 10 to 15 ml/kg with temperature of 34 to 36 oCelcius. TWBC is a mixture of blood and HTK kardioplegia with a composition of four to one. The outcomes of this study are malondialdehyde as a marker of reperfusion injury due to oxidative stress, caspase-3 as a marker of apoptosis, cTn-I as a marker of myocardial cell damage and the incidence of low cardiac output syndrome.
- Conditions
- Congenital Heart Disease
- Being tested
- Histidine Tryptophan Ketoglutarate Solution, Terminal Warm Blood Cardioplegia
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Histidine Tryptophan Ketoglutarate SolutionDrug
Hearts will be arrested with Histidine Tryptophan Ketoglutarate (HTK) solution during cardiac operation. After aortic cross clamp 50-60 ml/kg HTK will be administered
Terminal Warm Blood CardioplegiaOther
Also called Hot Shot
Terminal warm blood cardioplegia (TWBC) contains 20% HTK solution and 80% blood from cardiopulmonary bypass machine. Before aortic cross clamp removal 10-15 ml/kg TWBC will be administered with temperature 34-36 oCelcius
| Study group | Role | What they receive |
|---|---|---|
| HTK Solution | Active comparator | Hearts will be arrested with HTK solution during cardiac operation Receives: Drug: Histidine Tryptophan Ketoglutarate Solution |
| HTK Solution + TWBC | Active comparator | Hearts will be arrested with HTK solution during cardiac operation and received terminal warm blood cardioplegia before aortic cross clamp removal. Receives: Drug: Histidine Tryptophan Ketoglutarate Solution; Other: Terminal Warm Blood Cardioplegia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of Malondialdehyde levels
Malondialdehyde (MDA) is the end product of lipid peroxidation by ROS results in a state of oxidative stress, and a marker of the increase in ROS in reperfusion injury. MDA concentration in plasma of patients measured by test methods thiobarbituric acid and spectrophotometric examination.
Measured: after induction of anaesthesia, 30 minutes and 4 hours post aortic cross clamp removal
Change of Caspase-3 levels
Caspase-3 is a protease, a family of cysteine proteases that act as executor in the process of apoptosis, and is used as a marker of apoptosis. The expression of caspase-3 measured quantitatively by immunohistochemistry using polyclonal antibody method cleaved caspase-3 from myocardial biopsy.
Measured: after induction of anaesthesia, 30 minutes post aortic cross clamp removal
Cardiac Troponin I levels
Cardiac troponin I (cTnI) s a protein involved in the process of contraction of the heart, and is only found in heart cells, which will be released into the blood circulation when heart injury. CTn-I measured with Enzyme Linked Fluorescent Assay technique. Specimens for measurement of cTnI are from whole blood or serum.
Measured: During the first 24 hours after cross clamp removal
Number of patients with low cardiac output syndrome
Low cardiac output syndrome (LCOS) is a state in which clinical sign and symptoms of low cardiac output are found with or without the increasing of arterial and venous saturation gap and metabolic acidosis, the use of new inotropic, mechanical support, or other maneuvers in order to increase cardiac output. LCOS is determined by intensivist based on the clinical presentation, laboratory and inotropic scores.
Measured: During the first 48 hours after aortic cross clamp removal
Secondary outcomes (5)
Inotropic Score
Inotropic score is a method for determining the use of inotropic drugs used by the patient. inotropic scores obtained by the following formula: Wernowsky IS = dose dopamine (mcg/kg/min) + dose dobutamine (mcg/kg/min) + 100 x doses of epinephrine (mcg/kg/min)
Measured: During the first 72 hours post cross clamp removal
Postoperative Time to Extubation
Measured: up to 3 month after surgery
Postoperative Length of Stay in Intensive Care Unit
Measured: up to 3 month after surgery
Postoperative Hospital Length of Stay
Measured: up to 3 month after surgery
All cause mortality
Measured: up to 3 month after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2015 (estimated)
- Study startDec 2015
- Primary completionAug 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Heart 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
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cardiovascular Center Harapan Kita Hospital Indonesia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pribadi W Busro, MD, National Cardiovascular Center Harapan Kita Hospital Indonesia
- Investigators
- Pribadi W Busro, MD, Principal investigator, National Cardiac Centre Harapan Kita Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02618824
- Sponsor's protocol ID
- 01201508011
- Status last verified
- Dec 2015
- First submitted
- 23 Nov 2015
- Last updated
- 19 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Terminal Warm Blood Cardioplegia as Myocardial Protection in the Use of Histidine-Tryptophan-Ketoglutarate Cardioplegia in Complex Congenital Heart Surgery
- ClinicalTrials.gov ID
- NCT02618824
- Acronym / sponsor ID
- 01201508011
- Conditions
- Congenital Heart Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- National Cardiovascular Center Harapan Kita Hospital IndonesiaUniversity, hospital or other
- Study start
- Dec 2015
- Primary completion
- Aug 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 1 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Terminal warm blood cardioplegia (TWBC) has been shown to enhance myocardial protection in adult patients. Even in pediatric patients, the use of cold blood cardioplegia followed by administration of TWBC will provide cardioprotective effect similar to adult patients. Histidine-tryptophan-ketoglutarate (HTK), is attractive for cardiac surgeons because it is administered as a single dose and is claimed to offer myocardial protection for a period of up to 180 minutes allowing performance of complex procedures without interruption. Merging the use of TWBC on the use of HTK cardioplegia, especially for pediatric cardiac cases, have not been investigated. This technique is expected to provide a longer ischemic time and a protective effect against reperfusion injury.
Detailed description
The design of this study is a randomized controlled trial in children younger than 5 years old undergoing heart surgery with cardiopulmonary bypass. The objective of this study is to assess the role of TWBC in use of HTK cardioplegia compared with the use of HTK cardioplegia alone in open heart surgery of complex congenital heart disease. This study will be conducted at the National Cardiac Centre Harapan Kita Hospital Indonesia. Surgery will be performed in the operating room of Pediatric and Congenital Cardiac Surgery Unit. This study uses non-probability consecutive sampling. The samples are all pediatric patients with complex congenital heart disease who meet the inclusion criteria and not excluded by the exclusion criteria. Patients will be divided into two groups, the treatment group who received HTK cardioplegia and TWBC, and the control group that only received HTK cardioplegia alone. Hearts will be arrested with HTK solution during cardiac operation. HTK cardioplegia will be given through the aortic root at a dose of 50-60 ml/kg after aortic cross-clamped. For the treatment group, TWBC will be given shortly before the aortic cross clamp is removed at a dose of 10 to 15 ml/kg with temperature of 34 to 36 oCelcius. TWBC is a mixture of blood and HTK kardioplegia with a composition of four to one. The outcomes of this study are malondialdehyde as a marker of reperfusion injury due to oxidative stress, caspase-3 as a marker of apoptosis, cTn-I as a marker of myocardial cell damage and the incidence of low cardiac output syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HTK Solution | Active comparator | Drug: Histidine Tryptophan Ketoglutarate SolutionHearts will be arrested with HTK solution during cardiac operation |
| HTK Solution + TWBC | Active comparator | Drug: Histidine Tryptophan Ketoglutarate Solution, Other: Terminal Warm Blood CardioplegiaHearts will be arrested with HTK solution during cardiac operation and received terminal warm blood cardioplegia before aortic cross clamp removal. |
Who may qualify
- Ages
- Up to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Patient diagnosed with complex cyanotic congenital heart disease who scheduled for pediatric cardiac surgery
- Aristotle score is 8 and above
- Parents of patient have written informed consent and agree to follow the research procedures
Key exclusion criteria (2 listed)
- Patient diagnosed with an other congenital defect
- Patient diagnosed with rare congenital heart defect and high mortality rate (such as hypoplastic left heart syndrome)
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 |
|---|---|---|
| Histidine Tryptophan Ketoglutarate SolutionHearts will be arrested with Histidine Tryptophan Ketoglutarate (HTK) solution during cardiac operation. After aortic cross clamp 50-60 ml/kg HTK will be administered | Drug | HTK Solution, HTK Solution + TWBC |
| Terminal Warm Blood CardioplegiaAlso: Hot ShotTerminal warm blood cardioplegia (TWBC) contains 20% HTK solution and 80% blood from cardiopulmonary bypass machine. Before aortic cross clamp removal 10-15 ml/kg TWBC will be administered with temperature 34-36 oCelcius | Other | HTK Solution + TWBC |
Primary outcome
Change of Malondialdehyde levels
Time frame: after induction of anaesthesia, 30 minutes and 4 hours post aortic cross clamp removal
Malondialdehyde (MDA) is the end product of lipid peroxidation by ROS results in a state of oxidative stress, and a marker of the increase in ROS in reperfusion injury. MDA concentration in plasma of patients measured by test methods thiobarbituric acid and spectrophotometric examination.
Change of Caspase-3 levels
Time frame: after induction of anaesthesia, 30 minutes post aortic cross clamp removal
Caspase-3 is a protease, a family of cysteine proteases that act as executor in the process of apoptosis, and is used as a marker of apoptosis. The expression of caspase-3 measured quantitatively by immunohistochemistry using polyclonal antibody method cleaved caspase-3 from myocardial biopsy.
Cardiac Troponin I levels
Time frame: During the first 24 hours after cross clamp removal
Cardiac troponin I (cTnI) s a protein involved in the process of contraction of the heart, and is only found in heart cells, which will be released into the blood circulation when heart injury. CTn-I measured with Enzyme Linked Fluorescent Assay technique. Specimens for measurement of cTnI are from whole blood or serum.
Number of patients with low cardiac output syndrome
Time frame: During the first 48 hours after aortic cross clamp removal
Low cardiac output syndrome (LCOS) is a state in which clinical sign and symptoms of low cardiac output are found with or without the increasing of arterial and venous saturation gap and metabolic acidosis, the use of new inotropic, mechanical support, or other maneuvers in order to increase cardiac output. LCOS is determined by intensivist based on the clinical presentation, laboratory and inotropic scores.
5 secondary outcomes
Inotropic Score
Time frame: During the first 72 hours post cross clamp removal
Postoperative Time to Extubation
Time frame: up to 3 month after surgery
Postoperative Length of Stay in Intensive Care Unit
Time frame: up to 3 month after surgery
Postoperative Hospital Length of Stay
Time frame: up to 3 month after surgery
All cause mortality
Time frame: up to 3 month after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2016.
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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.
Pribadi W Busro, MD principal investigator
National Cardiac Centre Harapan Kita Hospital
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 Histidine Tryptophan Ketoglutarate Solution and Terminal Warm Blood Cardioplegia in people with Congenital Heart Disease, run by National Cardiovascular Center Harapan Kita Hospital Indonesia at 1 site in Indonesia.
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 3 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 19 Feb 2016. 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 Indonesia. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pribadi W Busro, MD (628128820719, pribadiwb@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Malondialdehyde levels (time frame: after induction of anaesthesia, 30 minutes and 4 hours post aortic cross clamp removal). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Feb 2016.