To evaluate the efficacy and safety of STS compared to placebo treatment on myocardial infarct size in patients presenting with STEMI and treated with PCI and in adjunction to optimal reperfusion therapy.
ID
Source
Brief title
Condition
- Myocardial disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is infarct size as measured with cardiac magnetic resonance
imaging (CMR-imaging) 4 months after randomization.
Secondary outcome
Secondary CMR-imaging efficacy measures include left ventricular ejection
fraction (LVEF) and myocardial perfusion reserve (MPR) at 4 month follow up.
Furthermore, N-terminal fragment brain natriuretic peptide (NT-proBNP) will be
assessed 4 months after randomisation. Other secondary efficacy endpoint
measures will be obtained from non-mandatory CMR-imaging during hospitalization
to study myocardial haemorrhage, microvascular obstruction (MVO) and myocardial
salvage index (MSI). Clinical safety endpoints include all-cause mortality and
combined incidence of cardiovascular events: cardiovascular death,
re-infarction, re-intervention and stroke. As additional safety endpoints we
will evaluate the incidence of internal cardiac defibrillator (ICD)
implantation and hospitalization for heart failure or chest pain. Finally,
enzymatic infarct size as assessed by peak creatine kinase, muscle-brain
isoenzymes (CK)-MB) during hospitalization will be used as very early safety
parameter.
Background summary
Timely and effective reperfusion by primary percutaneous coronary intervention
(PPCI) is currently the most effective treatment of ST-segment elevation
myocardial infarction (STEMI). However, permanent myocardial injury related to
the ischemia and subsequent reperfusion is observed in the vast majority (88%)
of patients and harbours a risk of heart failure development. Administration of
hydrogen sulfide (H2S) has been shown to protect the heart from *ischemia
reperfusion injury* in various experimental models. Data in humans suggests
that the H2S-releasing agent sodium thiosulfate (STS) can be administered
safely.
Study objective
To evaluate the efficacy and safety of STS compared to placebo treatment on
myocardial infarct size in patients presenting with STEMI and treated with PCI
and in adjunction to optimal reperfusion therapy.
Study design
This is a single-center, prospective, stratified, randomized double blind
study. In total, 380 patients with a first acute MI will be included. Before
PCI, all patients will be randomly assigned to receive either optimal standard
medical care or receive sodium thiosulfate on top of standard medical care. The
study will take place at the University Medical Center of Groningen, a center
with experience in primary PCI of patients with acute MI and with access to
emergency cardiac surgery. Four months after PCI, a period in which the
remodeling of the heart has completed, CMR-imaging is performed to determine
the infarct size. CMR is a well-recognized, validated, and highly reproducible
technique.
Intervention
Patients are randomised in an 1:1 ratio to be treated with STS 12.5g
intravenously (i.v.) or matched placebo immediately after arrival at the
catheterization laboratory (cath-lab) and a repeated dose administered 6 hours
after the first dose, on top of standard treatment.
Study burden and risks
Adverse effects on sodium thiosulfate: Reported side effects include nausea and
vomiting and can be controlled by anti-emetics. A less common side effect
metabolic acidosis appeared only in end-stage renal disease patients.
Hypernatraemia can occur after STS infusion, but was reported mild and
transient.
Adverse effects on intravenous contrast used during the MRI-scan (gadolinium)
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
1. Age * 18 years;, 2. The diagnosis STEMI defined by (1) chest pain suggestive
for myocardial ischemia for at least 30 minutes, the time from onset of the
symptoms less than 12 hours before hospital admission, and (2) an
electrocardiogram recording with ST- segment elevation of more than 0.1 mV in 2
or more contiguous leads or presence of new left bundle branch block;;, 3.
Symptoms and/or ST-segment deviation should be present (persisting) at time of
arrival in the catheterization laboratory;, 4. Primary percutaneous
intervention is being considered as treatment;, 5. Patient is willing to
cooperate with follow-up during 2 years.
Exclusion criteria
1. Prior myocardial infarction, unless maximum troponin T< 50 ng/L
(STEMI/non-STEMI/acute coronary syndrome);
2. Known permanent atrial fibrillation;
3. Prior CABG;
4. Prior PCI, complicated by periprocedural infarction, unless maximum troponin
T < 50ng/L;
5. Known cardiomyopathy;
6. Previous hospitalization for heart failure
7. Active malignancy (requiring chemotherapy, radiation or surgery at the time
of randomization), except for adequately treated non-melanoma skin cancer or
other noninvasive or in situ neoplasm (e.g., cervical cancer in situ);
8. History of chemotherapy;
9. History of radiotherapy in chest region;
10. Relieve of symptoms and complete ST-segment resolution prior to arrival at
the catheterization laboratory;
11. Presentation with cardiogenic shock (systolic blood pressure < 90 mmHg);
12. Severe hypertension (systolic blood pressure > 220 mmHg);
13. Sedated and/or intubated patients;
14. The existence of a condition with a life expectancy of less than 1 year;
15. Contraindication for 3 Tesla (T) CMR-imaging (e.g. body weight >;150kg;
known claustrophobia; 3T MRI incompatible ferromagnetic objects in the body,
end-stage renal disease);
16. Pregnancy or breastfeeding women; women of childbearing potential with
clinical suspicion of possible pregnancy;
17. A condition which, according to the clinical judgment of the investigator
and/or treating physician, does not allow the patient to successfully
participate in the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-001006-34-NL |
| ClinicalTrials.gov | NCT02899364 |
| CCMO | NL57899.042.16 |