Myocardial InjuryNCT05691764
Effect of Cyclosporine and Remote Ischemic Preconditioning in Reperfusion Ischemia Injury on Tetralogy Fallot Patients With Correction Surgery
A study testing Cyclosporin and remote ischemic preconditioning in people with Myocardial Injury and Cardiac Surgery, run by Universitas Indonesia at 1 site in Indonesia.
Trial summary
The study aimed to evaluate the combined effects of cyclosporine and remote ischemic preconditioning on MDA, calcium cytosol concentration, and mitochondrial edema in tetralogy Fallot patients undergoing corrective surgery. Read more about this study
- Who is it for?
- Ages 1 year to 6 years
- Conditions the study is for
- Myocardial Injury, Cardiac Surgery
- What is being tested?
- Cyclosporin and remote ischemic preconditioning
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteIndonesia
- Study dates
- 1 Sep 2020to 1 Sep 2022
- Phase
- Interventional
- 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 1 year to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Tetralogy Fallot patient that is undergoing correction surgery
- Has an ideal anatomy for corrective surgery, namely: Pulmonary artery size within normal limits (according to the kirklin table), Mc Goon ratio> 1.5, Nakata index> 200, normal coronary artery ostium and good biventricular function.
Who cannot join
- Patient refuses the procedure
- Patient with acute kidney injury
- Patient without lower extremity
- Patient with cyclosporin allergy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Cyclosporine and Remote Ischemic Preconditioning on MDA, Calcium Cytosol Concentration, and Mitochondrial Edema in Reperfusion Ischemia Injury: Research on Tetralogy Fallot Patients With Correction Surgery
The study aimed to evaluate the combined effects of cyclosporine and remote ischemic preconditioning on MDA, calcium cytosol concentration, and mitochondrial edema in tetralogy Fallot patients undergoing corrective surgery.
Read the detailed description
Forty patients undergoing tetralogy Fallot corrective surgery were randomized to RIPC and cyclosporine (n=20) and control (n=20). Cyclosporin was administered 2 hour pre induction of anesthesia with the dose of 3 mg/kg body weight intravenously. RIPC was performed preoperatively after induction of anesthesia by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval. Blood samples from coronary sinus and biopsies from the myocardial infundibulum were obtained three times at the condition of pre ischemic, ischemic, and reperfusion. MDA was measured from the blood samples, meanwhile calcium cytosol concentration and mitochondrial edema was measured from the biopsy samples.
- Conditions
- Myocardial Injury, Cardiac Surgery
- Being tested
- Cyclosporin, remote ischemic preconditioning, Placebo
- Keywords
- RIPC, cyclosporine, ischemia reperfusion injury, MDA, calcium cytosol, tetralogy Fallot, mitochondrial edema, infundibulum
- Medical subject headings
- Reperfusion Injury, Tetralogy of Fallot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclosporinDrug
Also called Sandimmun
Cyclosporin was administered intravenously with the dose of 3 mg/ kg body weight
remote ischemic preconditioningProcedure or surgery
Also called RIPC
Performed by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval
PlaceboDrug
Intravenous placebo
| Study group | Role | What they receive |
|---|---|---|
| Cyclosporin + RIPC | Experimental | This group received cyclosporin intravenously 2 hours pre-induction of anesthesia, with the dose of 3 mg/ kg body weight. RIPC was performed preoperatively after induction of anesthesia by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval. Receives: Drug: Cyclosporin; Procedure: remote ischemic preconditioning |
| Control | Placebo comparator | This group received placebo intravenously 2 hours pre-induction of anesthesia. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Malondialdehyde (MDA)
ROS level is determined by measuring MDA concentration (nmol/mL)
Measured: 1 year
Calcium cytosol concentration
Calcium concentration (nmol/mL) in cytosol is determined by ratiometric analysis on Fura Red- dyed heart cells.
Measured: 1 year
Mitochondrial edema
Mitochondrial edema (%) is measured by decreasing of optical density that indicates change in mitochondrial matrix volume.
Measured: 1 year
Secondary outcomes (4)
Cardiac index
Examined with echocardiography, unit of measurement is litres per minute per square metre (L/min/m2).
Measured: 1 year
Troponin I
Measured from venous blood, unit of measurement is nanograms per milliliter (ng/mL).
Measured: 1 year
Creatine kinase- MB (CKMB)
Measured from venous blood, unit of measurement is units per liter (IU/L).
Measured: 1 year
Vasoactive inotropic score (VIS)
VIS was calculated as: dopamine dose (μg/kg/min) + dobutamine dose (μg/kg/min) + 100 × epinephrine dose (μg/kg/min) + 10 × milrinone dose (μg/kg/min) + 10 000 × vasopressin dose (unit/kg/min) + 100 × norepinephrine dose (μg/kg/min).
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2023
- Study start1 Sep 2020
- Primary completion1 Dec 2021
- Study completion1 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Myocardial InjuryStudies of the same condition, open and under way.
- More trials run by Universitas IndonesiaThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitas Indonesia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jefferson K Hidayat, Universitas Indonesia
- Investigators
- Jefferson K Hidayat, MD, Principal investigator, Universitas Indonesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05691764
- Sponsor's protocol ID
- IndonesiaUAnes055
- Status last verified
- Jan 2023
- First submitted
- 15 Dec 2022
- Last updated
- 20 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wu Q, Wang T, Chen S, Zhou Q, Li H, Hu N, Feng Y, Dong N, Yao S, Xia Z. Cardiac protective effects of remote ischaemic preconditioning in children undergoing tetralogy of fallot repair surgery: a randomized controlled trial. Eur Heart J. 2018 Mar 21;39(12):1028-1037. doi: 10.1093/eurheartj/ehx030.
PubMed 28329231Davidson SM, Ferdinandy P, Andreadou I, Botker HE, Heusch G, Ibanez B, Ovize M, Schulz R, Yellon DM, Hausenloy DJ, Garcia-Dorado D; CARDIOPROTECTION COST Action (CA16225). Multitarget Strategies to Reduce Myocardial Ischemia/Reperfusion Injury: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Jan 8;73(1):89-99. doi: 10.1016/j.jacc.2018.09.086.
PubMed 30621955Zalewski J, Claus P, Bogaert J, Driessche NV, Driesen RB, Galan DT, Sipido KR, Buszman P, Milewski K, Van de Werf F. Cyclosporine A reduces microvascular obstruction and preserves left ventricular function deterioration following myocardial ischemia and reperfusion. Basic Res Cardiol. 2015 Mar;110(2):18. doi: 10.1007/s00395-015-0475-8. Epub 2015 Feb 27.
PubMed 25720581Chen HW, Chien CT, Yu SL, Lee YT, Chen WJ. Cyclosporine A regulate oxidative stress-induced apoptosis in cardiomyocytes: mechanisms via ROS generation, iNOS and Hsp70. Br J Pharmacol. 2002 Nov;137(6):771-81. doi: 10.1038/sj.bjp.0704908.
PubMed 12411407
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Cyclosporine and Remote Ischemic Preconditioning on MDA, Calcium Cytosol Concentration, and Mitochondrial Edema in Reperfusion Ischemia Injury: Research on Tetralogy Fallot Patients With Correction Surgery
- ClinicalTrials.gov ID
- NCT05691764
- Acronym / sponsor ID
- IndonesiaUAnes055
- Conditions
- Myocardial Injury, Cardiac Surgery
- Keywords
- RIPC, cyclosporine, ischemia reperfusion injury, MDA, calcium cytosol, tetralogy Fallot, mitochondrial edema, infundibulum
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Universitas IndonesiaUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 1 Dec 2021 (actual)
- Study completion
- 1 Sep 2022 (actual)
- First posted
- 20 Jan 2023 (actual)
- 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.
The study aimed to evaluate the combined effects of cyclosporine and remote ischemic preconditioning on MDA, calcium cytosol concentration, and mitochondrial edema in tetralogy Fallot patients undergoing corrective surgery.
Detailed description
Forty patients undergoing tetralogy Fallot corrective surgery were randomized to RIPC and cyclosporine (n=20) and control (n=20). Cyclosporin was administered 2 hour pre induction of anesthesia with the dose of 3 mg/kg body weight intravenously. RIPC was performed preoperatively after induction of anesthesia by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval. Blood samples from coronary sinus and biopsies from the myocardial infundibulum were obtained three times at the condition of pre ischemic, ischemic, and reperfusion. MDA was measured from the blood samples, meanwhile calcium cytosol concentration and mitochondrial edema was measured from the biopsy samples.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyclosporin + RIPC | Experimental | Drug: Cyclosporin, Procedure: remote ischemic preconditioningThis group received cyclosporin intravenously 2 hours pre-induction of anesthesia, with the dose of 3 mg/ kg body weight. RIPC was performed preoperatively after induction of anesthesia by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval. |
| Control | Placebo comparator | Drug: PlaceboThis group received placebo intravenously 2 hours pre-induction of anesthesia. |
Who may qualify
- Ages
- 1 year to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Tetralogy Fallot patient that is undergoing correction surgery
- Has an ideal anatomy for corrective surgery, namely: Pulmonary artery size within normal limits (according to the kirklin table), Mc Goon ratio> 1.5, Nakata index> 200, normal coronary artery ostium and good biventricular function.
Key exclusion criteria (4 listed)
- Patient refuses the procedure
- Patient with acute kidney injury
- Patient without lower extremity
- Patient with cyclosporin allergy
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 |
|---|---|---|
| CyclosporinAlso: SandimmunCyclosporin was administered intravenously with the dose of 3 mg/ kg body weight | Drug | Cyclosporin + RIPC |
| remote ischemic preconditioningAlso: RIPCPerformed by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval | Procedure or surgery | Cyclosporin + RIPC |
| PlaceboIntravenous placebo | Drug | Control |
Primary outcome
Malondialdehyde (MDA)
Time frame: 1 year
ROS level is determined by measuring MDA concentration (nmol/mL)
Calcium cytosol concentration
Time frame: 1 year
Calcium concentration (nmol/mL) in cytosol is determined by ratiometric analysis on Fura Red- dyed heart cells.
Mitochondrial edema
Time frame: 1 year
Mitochondrial edema (%) is measured by decreasing of optical density that indicates change in mitochondrial matrix volume.
4 secondary outcomes
Cardiac index
Time frame: 1 year
Troponin I
Time frame: 1 year
Creatine kinase- MB (CKMB)
Time frame: 1 year
Vasoactive inotropic score (VIS)
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2023.
- Results publication: PubMed 28329231Wu Q, Wang T, Chen S, Zhou Q, Li H, Hu N, Feng Y, Dong N, Yao S, Xia Z. Cardiac protective effects of remote ischaemic preconditioning in children undergoing tetralogy of fallot repair surgery: a randomized controlled trial. Eur Heart J. 2018 Mar 21;39(12):1028-1037. doi: 10.1093/eurheartj/ehx030.
- Results publication: PubMed 30621955Davidson SM, Ferdinandy P, Andreadou I, Botker HE, Heusch G, Ibanez B, Ovize M, Schulz R, Yellon DM, Hausenloy DJ, Garcia-Dorado D; CARDIOPROTECTION COST Action (CA16225). Multitarget Strategies to Reduce Myocardial Ischemia/Reperfusion Injury: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Jan 8;73(1):89-99. doi: 10.1016/j.jacc.2018.09.086.
- Results publication: PubMed 25720581Zalewski J, Claus P, Bogaert J, Driessche NV, Driesen RB, Galan DT, Sipido KR, Buszman P, Milewski K, Van de Werf F. Cyclosporine A reduces microvascular obstruction and preserves left ventricular function deterioration following myocardial ischemia and reperfusion. Basic Res Cardiol. 2015 Mar;110(2):18. doi: 10.1007/s00395-015-0475-8. Epub 2015 Feb 27.
- Results publication: PubMed 12411407Chen HW, Chien CT, Yu SL, Lee YT, Chen WJ. Cyclosporine A regulate oxidative stress-induced apoptosis in cardiomyocytes: mechanisms via ROS generation, iNOS and Hsp70. Br J Pharmacol. 2002 Nov;137(6):771-81. doi: 10.1038/sj.bjp.0704908.
- Individual participant dataSharing planned: No
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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.
Jefferson K Hidayat, MD principal investigator
Universitas Indonesia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cyclosporin and remote ischemic preconditioning in people with Myocardial Injury and Cardiac Surgery, run by Universitas 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 2 inclusion and 4 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 20 Jan 2023. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Malondialdehyde (MDA) (time frame: 1 year). 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 NCT05691764, which also lists 4 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 20 Jan 2023.