Patients are divided in 6 groups of 3 patients to receive the following intervention: 0 gram (g), 2.5 g, 5 g, 10 g, 12.5 g and 15 g of sodium thiosulfate pentahydrate (STS) intravenous. The first dose is given in 15 min immediately after inclusion at the cath-lab. In the absence of dose-limiting toxicity (DLT), a second gift of STS is given in 30 min, 6 hours later at the coronary care unit (CCU). When no DLT is observed in any of the patients after 2 gifts of the same dose an extra 3 subjects are enrolled into the next higher dose cohort. If 1 out of 3 patient develops DLT at a specific dose, an extra 3 subjects are enrolled into the same dose cohort. When more than 1 out of 6 patients develop DLT the trial will be terminated because the maximum tolerable dose (MTD) has been exceeded.

Acute Coronary Syndrome

Sodium Thiosulfate Pentahydrate is administered intravenously in 250 centiliters infusion fluid in two doses: first dose with an infusion rate of 16.66 milliliter (ml) per minute (min), second dose with 8.33 ml / min

Sodium Thiosulfate Pentahydrate

University Medical Centre Groningen

Safety and Tolerability of Sodium Thiosulfate in Patients With an ACS Undergoing CAG Via Trans-radial Approach.

Safety and Tolerability of Sodium Thiosulfate in Patients Presenting With an Acute Coronary Syndrome Undergoing Coronary Angiography Via Trans-radial Approach: a Dose-escalation Study.

DLT defined as all-cause mortality or hemodynamic instability of significant clinical impact:
Hemodynamic instability of significant clinical impact is defined as:
Systolic blood pressure <90 millimeters mercury (mmHg) 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:
Confusion;
Cool, clammy skin;
Oliguria (urine output <30 ml/h);
Serum-lactate >2.0 mmol/l.
Shock of other causes (hypovolemia, sepsis, bradycardia) are ruled out.

Severe hypersensitivity/allergic reaction such as angio-edema, heavy itch/rash. Outcome measurement will assessed using a binary scale: present (yes) or absent (no)

using a 4-point Likert-scale: 0= none, 1= nauseated but able to eat and/or 1 episode of vomiting in 24 hours, 2= food intake significantly decreased and/or 2-5 episodes of vomiting in 24 hours, 3= intravenous fluids required and/or >5 episodes of vomiting in 24 hours

effect of STS on oxidative stress markers in blood by laboratory analysis of free thiols in blood. Unity: µmol/l. Measurement on different timeframes, starting at T=0, to evaluate the effect of STS on free thiol levels in blood.

Pim van der Harst

Prof. dr.

University Medical Center Groningen

25 gram sodium thiosulfate is given intravenously in two doses of 12.5 gram (50mL) dissolved in 250 ml sodium chloride 0.9%. Upon arrival at the cath-lab, after confirming in- and exclusion criteria and obtaining verbal informed consent the first dose, will be administered in 20 minutes (infusion rate 15 mL/min). After infusion the patient will receive primary percutaneous coronary intervention. Post-PCI the patient will be admitted to the coronary care unit where he will receive the second dose, 6 hours after start of the first dose. The second dose is administered in 30 minutes (infusion rate 10 mL/min). At 4 months infarct size is assessed by LGE cardiac magnetic resonance imaging.

50 ml Sodium chloride 0.9%, added to 250ml sodium chloride 0.9% is administered twice. Upon arrival at the cath-lab, after confirming in- and exclusion criteria and obtaining verbal informed consent the first dose, will be administered in 20 minutes (infusion rate 15ml/min). After infusion the patient will receive primary percutaneous coronary intervention. Post-PCI the patient will be admitted to the coronary care unit where he receive the second dose, 6 hours after start of the first dose. The second dose is administered in 30 minutes (infusion rate 10 mL/min). At 4 months infarct size is assessed by LGE cardiac magnetic resonance imaging.

Myocardial Infarction

Heart Failure

Sodium thiosulfate

see description under placebo comparator arm

Sodium chloride 0.9%

Primary treatment of the ischemia-related coronary artery is left to discretion of the operator and might consist of thrombus aspiration, balloon inflation and stent implantation. Additional balloon angioplasty or stenting of the culprit or other lesions will be performed when necessary.

primary percutaneous coronary intervention

CMR-imaging will be used for assessment of infarct size, left ventricular function, quantification of myocardial scar and diffuse myocardial fibrosis. CMR-imaging examinations will be performed on a 3 Tesla scanner using a phased array cardiac receiver coil at 4 months after randomization according to standard protocols. The full study protocol lasts approximately 45 minutes and includes anatomy and function, LGE and T1-mapping.

cardiac magnetic resonance imaging

Treant Scheper Hospital

Sodium Thiosulfate to Preserve Cardiac Function in STEMI

Groningen Intervention Study for the Preservation of Cardiac Function With Sodium Thiosulfate After ST-segment Elevation Myocardial Infarction

Safety parameter. Includes cardiovascular mortality, re-infarction, re-intervention (any revascularization not planned on index CAG), stroke.

Safety parameter. defined as an overnight stay, with different dates for admission and discharge

Health related quality of life assessed using the EuroQol EQ-5D-5L.
The EQ-5D-5L has 2 components:
There is a descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, unable/extreme problems. The respondent is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.
The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'.
The users guide gives details of the scoring system: https://euroqol.org/wp-content/uploads/2016/09/EQ-5D-5L_UserGuide_2015.pdf

Assessed with PANAS questionnaire (Positive And Negative Affect Schedule), positive affect score can range from 10 to 50, with higher scores representing higher positive affective state; negative affect score ranges from 10 to 50 with lower scores representing lower levels of negative affect

Analysis of primary and secondary endpoints according to important risk factors and known medical history collected during routine clinical care for STEMI.

Changes include incidence of new Q waves, ST-segment resolution, persistent ST-deviation.

MD, PhD

Inspired oxygen fraction > 0.5 and SpO2 = 98-100%

Air or lowest possible inspired concentration of oxygen to maintain SpO2 > 90%

Vascular Disease

Oxygen in sufficient quantity to maintain SpO2 > 98%

Oxygen

Supplemental Oxygen in sufficient quantity to maintain SpO2 > 90%

cyanide/infarkts

Safety and Tolerability of Sodium Thiosulfate in Patients With an ACS Undergoing CAG Via Trans-radial Approach.

Sodium Thiosulfate to Preserve Cardiac Function in STEMI

Is Peri-operative Hyperoxemia a Risk Factor for Postoperative Complications?

Therapeutic Application of Intravascular Nitrite for Sickle Cell Disease

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