Hydrogen sulfide (H2S)-donor sodium thiosulfate (STS) did not reduce infarct size versus placebo in patients presenting with ST-segment elevation myocardial infarction (STEMI) in the Phase II GIPS-IV trial. However, the results do not exclude H2S as a potential cardioprotective therapy, said the study’s lead author, Marie-Sophie L.Y. de Koning, MD, of University Medical Center Groningen, the Netherlands. She presented the results Monday at the American College of Cardiology’s 71st Annual Scientific Session in Washington, D.C. Myocardial infarction (MI) is still a major risk factor for heart failure and early mortality, de Koning said in her presentation, marking infarct size as the strongest predictor of clinical outcomes. H2S is currently used for the treatment of cyanide poisoning, the rare vascular condition calciphylaxis, and to alleviate side effects from cisplatin chemotherapy. Its potential for protecting the heart from ischemia-reperfusion injury has also been demonstrated in various preclinical studies, attributed to its anti-inflammatory, antioxidant and vasodilatory properties, including a cellular cardiomyocytes model study. GIPS-IV was, therefore, set up as the first clinical trial to test H2S-donor STS in the STEMI setting, specifically on whether the treatment could reduce myocardial infarct size compared to placebo 4 months after randomization as measured by magnetic resonance imaging (MRI). Secondary endpoints included the effect of STS on peak creatine kinase-MB (CK-MB) during the index event, plus left ventricular ejection fraction (LVEF), N-terminal pro-brain natriuretic peptide (NT-prBNP) levels and major adverse cardiovascular events (MACE) at 4 months follow-up. The double-blind, randomized multicenter trial randomized 373 adult patients with a first STEMI between July 2018 and March 2021 treated at three Dutch sites, randomizing them to receive either 12.5 g of STS intravenously (186 patients) or matching placebo (187 patients) immediately on arrival at the catheterization laboratory, and again 6 hours later. The patients’ mean age was 62 years for both groups, they were majority male (25% female in STS and 21% in placebo), were 97% Caucasian in both groups respectively, and all had onset of complaints <12 hours before arrival at the cath lab. Ischemic time was a mean of 133 minutes in the STS group – of which 66% had single-vessel disease – and 147 minutes for placebo patients, where 49% had single-vessel disease. Those with prior MI, coronary artery bypass graft (CABG) or cardiomyopathy were excluded. There was no significant difference in infarct sizes between the two groups at 4 months (STS 8% vs. placebo 8.9%; P = 0.55).