to evaluate the safety and maximum tolerable dose of sodium thiosulfate in patients presenting with acute coronary syndrome undergoing coronary angiography via transradial approach, when given in combination with concomitant vasodilator drugs.
ID
Source
Brief title
Condition
- Myocardial disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is the development of DLT:
All-cause mortality OR hemodynamic instability developed during STS
administration, in combination with vasodilators used in radial approach and/or
during second infusion after 6 hours. Hemodynamic instability of significant
clinical impact is defined as :
- Systolic blood pressure <90mmHg for >30 min and/or
- Catecholamines required to maintain pressure >90 mmHg during systole and
- Signs of pulmonary congestion or elevated left-ventricular filling pressures,
and
- Signs of impaired organ perfusion with *1 of the following criteria:
o Confusion;
o Cool, clammy skin;
o Oliguria (urine output <30 ml/h);
o Serum-lactate >2.0 mmol/l.
- Shock of other causes (hypovolemia, sepsis, bradycardia) are ruled out.
Secondary outcome
The effect of STS on:
- the development of anaphylaxis;
- Nausea/vomiting;
- Oxidative stress markers
Background summary
timely and effective reperfusion by primary percutaneous coronary intervention
(PPCI) is currently the most effective treatment of acute coronary syndrome
(ACS). However, permanent myocardial injury related to the ischemia and
subsequent reperfusion is observed in most 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. A dose of 25 gram/day can be safely applied in other
patient groups (haemodialysis patients, paediatric cancer patients treated with
chemotherapy). However, the safety and tolerability of H2S have never been
tested in ACS patients. These patients are given blood pressure lowering and
vasodilating drugs which can potentially interact with H2S. Data regarding the
dose-limiting toxicity (DLT) and maximum tolerable dose (MTD) of H2S in the
clinical setting of ACS is needed before H2S can be tested in a randomized
clinical trial.
Study objective
to evaluate the safety and maximum tolerable dose of sodium thiosulfate in
patients presenting with acute coronary syndrome undergoing coronary
angiography via transradial approach, when given in combination with
concomitant vasodilator drugs.
Study design
a single centre, open label dose-escalation study with a 3+3 design with fixed
dosing endpoint.
Intervention
the patients will receive STS i.v. in different doses (0, 2.5, 5, and 10 g,
12.5 and 15g; 3 patients per dose cohort). STS is administered immediately
after arrival at the catheterization laboratory (cath-lab). If hemodynamic
stable, a second gift of STS is administered 6 hours after the first dose at
the coronary care unit (CCU). When no DLT is observed in any of the patients
after two gifts we will enrol 3 additional subjects into the next higher dose
cohort. If 1 out of 3 patient suffers hemodynamic instability for 30 minutes at
a specific dose, an additional 3 subjects are enrolled into the same dose
cohort. When more than 1 out of 6 patients develop DLT this implies that the
MTD has been exceeded and the trial is terminated.
Blood samples will be taken at presentation and 3 hours after each injection to
evaluate the effect of STS on various oxidative stress markers.
Study burden and risks
The burden for the patient is low. Patients are usually admitted at the
hospital during the first 48 hours. All patients receive an extra intravenous
catheter at the catheterization lab, upon which they receive STS treatment.
Blood samples will be taken from a different catheter for the measurement of
oxidative stress markers. The anticipated risks for the patients are possible
refractory hypotension, severe hypersensitivity reaction, sever renal
dysfunction, and bleeding complications.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
- Age * 18 years;
-The diagnosis ACS defined by: chest pain suggestive for myocardial ischemia for at least 30 minutes, the time from onset of the symptoms less than 24 hours before hospital admission, with (STEMI) or without (nSTEMI/iAP) an electrocardiogram (ECG) recording with ST- segment elevation of more than 0.1 mV in 2 or more contiguous leads;
-cardiac catheterization via radial approach is being considered;
- Patient is willing to cooperate with the trial during hospitalization.
Exclusion criteria
- Known cardiomyopathy or LVEF < 35%;
- History of a malignancy treated with chemo- and/or radiotherapy < 1 year;
- Systolic blood pressure under 100mmHg or over 180mmHg at presentation;
- Cardiogenic shock at presentation? (def: SHOCK II)
- Sedated and/or intubated patients;
- The existence of a condition with a life expectancy of less than 1 year;
- pregnant or breastfeeding at time of presentation;
- 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 | EUCTR2017-000203-25-NL |
| ClinicalTrials.gov | NCT03017963 |
| CCMO | NL60193.042.17 |