Rationale and Design of the Groningen Intervention Study for the Preservation of Cardiac Function with Sodium Thiosulfate after St-segment Elevation Myocardial Infarction (GIPS-IV) trial

• Published in: The American heart journal 2022-01, Vol.243, p.167-176
• Main Authors: de Koning, Marie-Sophie LY, van Dorp, Paulien, Assa, Solmaz, Hartman, Minke HT, Voskuil, Michiel, Anthonio, Rutger L, Veen, Duco, Pundziute-Do Prado, Gabija, Leiner, Tim, van Goor, Harry, van der Meer, Peter, van Veldhuisen, Dirk J, Nijveldt, Robin, Lipsic, Erik, van der Harst, Pim
• Format: Article
• Language: English
• Subjects: Acute coronary syndrome; Acute coronary syndromes; Animal models; Cardiac function; Cardiomyocytes; Cardioprotection; Catheterization; Clinical trials; Good Manufacturing Practice; Heart; Heart attacks; Heart failure; Hospitalization; Humans; Hydrogen sulfide; Injury prevention; Intubation; Ischemia; Ischemia-reperfusion injury; Laboratories; Magnetic resonance imaging; Mortality; Myocardial Infarction; Patients; Percutaneous Coronary Intervention; Pharmacy; Placebos; Preservation; Quality of life; Questionnaires; Randomization; Reperfusion; Segments; Sodium; Sodium thiosulfate; ST Elevation Myocardial Infarction - drug therapy; Stroke Volume; Thiosulfate; Thiosulfates; Treatment Outcome; Ventricle; Ventricular Function, Left; Vital signs
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2021.08.012

Ischemia and subsequent reperfusion cause myocardial injury in patients presenting with ST-segment elevation myocardial infarction (STEMI). Hydrogen sulfide (H2S) reduces “ischemia-reperfusion injury” in various experimental animal models, but has not been evaluated in humans. This trial will examine the efficacy and safety of the H2S-donor sodium thiosulfate (STS) in patients presenting with a STEMI. The Groningen Intervention study for the Preservation of cardiac function with STS after STEMI (GIPS-IV) trial (NCT02899364) is a double-blind, randomized, placebo-controlled, multicenter trial, which will enroll 380 patients with a first STEMI. Patients receive STS 12.5 grams intravenously or matching placebo in addition to standard care immediately at arrival at the catheterization laboratory after providing consent. A second dose is administered 6 hours later at the coronary care unit. The primary endpoint is myocardial infarct size as quantified by cardiac magnetic resonance imaging 4 months after randomization. Secondary endpoints include the effect of STS on peak CK-MB during admission and left ventricular ejection fraction and NT-proBNP levels at 4 months follow-up. Patients will be followed-up for 2 years to assess clinical endpoints. The GIPS-IV trial is the first study to determine the effect of a H2S-donor on myocardial infarct size in patients presenting with STEMI.