Sodium Thiosulfate to Preserve Cardiac Function in STEMI

NCT02899364 | Unknown Phase 2 DMC

• 2 other identifiers: GIPS-IV2015-001006-34
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 3

Brief Summary

Rationale: 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. 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 Study design: a multicenter, double blind, randomized controlled clinical trial. A total of 380 patients, aged 18 years and above, undergoing primary PCI for a first STEMI and deemed amenable, by the investigator, 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. Primary endpoint is infarct size as measured with cardiac magnetic resonance imaging (CMR-imaging) 4 months after randomization.

Conditions

Myocardial Infarction; Heart Failure

Keywords

Sodium thiosulfate; STEMI; Infarct size; Cardiac magnetic resonance imaging; Hydrogen sulfide

Outcome Measures

Primary Outcomes (1)

• Myocardial infarct size as measured with late gadolinium enhancement cardiac magnetic resonance imaging.

  Primary efficacy parameter

  4 months after randomization

Secondary Outcomes (9)

• Left ventricular ejection fraction as assessed by cardiac magnetic resonance imaging

  4 months after randomization

• N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level (ng/L)

  4 months after randomization

• All cause mortality

  4 months after randomization and after 2-year follow-up

• Combined major adverse cardiovascular events

  4 months after randomization and after 2-year follow-up

• Incidence of stroke

  4 months after randomization and after 2-year follow-up

Other Outcomes (6)

• Health related quality of life: EuroQol EQ-5D-5L

  0-5 days after randomization (during hospitalization) and at 4 months follow up

• General affective status

  0-5 days after randomization (during hospitalization) and at 4 months follow up

• Creatine Kinase (U/L)

  0-3 days after randomization (during hospitalization)

Study Arms (2)

Sodium thiosulfate

EXPERIMENTAL

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.

Drug: Sodium thiosulfate; Procedure: primary percutaneous coronary intervention; Other: cardiac magnetic resonance imaging

Sodium chloride 0.9%

PLACEBO COMPARATOR

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.

Drug: Sodium chloride 0.9%; Procedure: primary percutaneous coronary intervention; Other: cardiac magnetic resonance imaging

Interventions

Sodium thiosulfate DRUG

see description under experimental arm

Sodium thiosulfate

Sodium chloride 0.9% DRUG

see description under placebo comparator arm

Also known as: Placebo

Sodium chloride 0.9%

primary percutaneous coronary intervention PROCEDURE

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.

Also known as: PPCI

Sodium chloride 0.9%; Sodium thiosulfate

cardiac magnetic resonance imaging OTHER

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.

Also known as: CMR-imaging

Sodium chloride 0.9%; Sodium thiosulfate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years;
• 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 (ECG) recording with ST- segment elevation of more than 0.1 millivolt (mV) in 2 or more contiguous leads or presence of new left bundle branch block;
• Symptoms and/or ST-segment deviation should be present (persisting) at time of arrival in the cath-lab;
• Primary PCI is being considered as treatment;
• Patient is willing to cooperate with follow-up during 2 years.

You may not qualify if:

• Prior MI (STEMI/non-STEMI/acute coronary syndrome (ACS), unless maximum troponin T \< 50ng/L.
• Prior CABG;
• Prior PCI, complicated by periprocedural infarction, unless maximum troponin T \< 50 ng/L;
• Known cardiomyopathy;
• Previous hospitalization for heart failure;
• 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);
• History of chemotherapy;
• History of radiotherapy in chest region;
• Relieve of symptoms and complete ST-segment resolution prior to arrival at the cath-lab;
• Known permanent atrial fibrillation;
• Presentation with cardiogenic shock (systolic blood pressure \<90 mmHg);
• Severe hypertension (systolic blood pressure \>220 mmHg);
• Sedated and/or intubated patients;
• The existence of a condition with a life expectancy of less than 1 year;
• Contraindication for 3 Tesla (T) CMR-imaging (e.g. body weight \>150kg; known claustrophobia; 3 T magnetic resonance imaging (MRI) incompatible ferromagnetic objects in the body, end-stage renal disease);

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (3)

Treant Scheper Hospital

Emmen, Drenthe, 7824 AA, Netherlands

Location

University Medical Centre Groningen

Groningen, 9700RB, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (1)

• de Koning ML, van Dorp P, Assa S, Hartman MH, Voskuil M, Anthonio RL, Veen D, Pundziute-Do Prado G, Leiner T, van Goor H, van der Meer P, van Veldhuisen DJ, Nijveldt R, Lipsic E, van der Harst P. 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. Am Heart J. 2022 Jan;243:167-176. doi: 10.1016/j.ahj.2021.08.012. Epub 2021 Sep 15.

  PMID: 34534493 DERIVED

MeSH Terms

Conditions

Myocardial Infarction; Heart Failure; ST Elevation Myocardial Infarction

Interventions

sodium thiosulfate; Sodium Chloride

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Pim van der Harst, Prof. dr.

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: August 31, 2016
• First Posted: September 14, 2016
• Study Start: July 20, 2018
• Primary Completion: June 25, 2021
• Study Completion: March 1, 2023
• Last Updated: September 9, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3)