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Sodium Thiosulfate to Preserve Cardiac Function in STEMI (GIPS-IV)

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ClinicalTrials.gov Identifier: NCT02899364
Recruitment Status : Not yet recruiting
First Posted : September 14, 2016
Last Update Posted : September 14, 2016
Sponsor:
Information provided by (Responsible Party):
Carlijn Maagdenberg, University Medical Center Groningen

Brief Summary:

Rationale: the cornerstone treatment of a heart attack is a procedure called primary percutaneous coronary intervention (PPCI): the cardiologist uses a catheter and guides it through an artery, mostly the wrist artery, to the site of the narrowing in the coronary artery in the heart and opens it with a balloon. Thereafter a small metal tube is placed at the site of the narrowing to keep the artery open). However, a heart attack still leads to irreversible injury to the heart with a risk of heart failure. The investigators have evidence from (cell/animal) that administration of hydrogen sulfide (H2S), which is also made in the human body, has been shown to protect the heart muscle and organs from damage caused by the lack of oxygen resulting from a heart attack. Data in humans suggests that sodium thiosulfate (STS) (a medicine that releases H2S in the body, and is already used to treat other diseases, i.e. cyanide poisoning and renal failure associated diseases) can be administered safely.

Objective: to evaluate if sodium thiosulfate protects the heart from damage caused by a heart attack.

Study design: a single centre, double blind (both doctor and patient do not know which treatment patient gets), randomized controlled clinical trial.

A total of 380 patients, aged 18 years and above, undergoing treatment for a first heart attack are divided in two groups (decided by chance): 1 group receives sodium thiosulfate, the other receives a fake medicine (salt water that looks exactly like sodium thiosulfate).

After 4 months patients receive a magnetic scan of the heart to evaluate the permanent damage of the heart muscle. When comparing the patients from both groups to each other the investigators can say something about the effectivity sodium thiosulfate.


Condition or disease Intervention/treatment Phase
Myocardial Infarction Heart Failure Drug: Sodium thiosulfate Drug: sodium chloride (NaCl) Procedure: primary percutaneous coronary intervention Other: cardiac magnetic resonance imaging Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 380 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Groningen Intervention Study for the Preservation of Cardiac Function With Sodium Thiosulfate After ST-segment Elevation Myocardial Infarction
Study Start Date : September 2016
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sodium thiosulfate
25 gram sodium thiosulfate is given intravenously in two doses of 12.5 gram in 250 cc. After arrival at the cath-lab, confirming STEMI and obtaining verbal informed consent the first dose, will be administered in 15 minutes (infusion rate 16.66 mL/min). After infusion the patient will receive primary percutaneous coronary intervention. Post-PCI they will be submitted to the cardiac control unit where they receive the second dose, 6 hours after start of the first dose. The second dose is administered in 30 minutes (infusion rate 8.33 mL/min). At 4 months infarct size is assessed by LGE cardiac magnetic resonance imaging.
Drug: Sodium thiosulfate
see description under experimental arm

Procedure: primary percutaneous coronary intervention
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.
Other Name: PPCI

Other: cardiac magnetic resonance imaging
CMR-imaging will be used for assessment of 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{33}. The full study protocol lasts approximately 45 minutes and includes anatomy and function, LGE and T1-mapping.
Other Name: CMR-imaging

Placebo Comparator: Sodium Chloride
Sodium chloride is given as placebo in two doses of 250cc. After arrival at the cath-lab, confirming STEMI and obtaining oral informed consent the first dose, will be administered in 15 minutes (infusion rate 16.66ml/min). After infusion the patient will receive primary percutaneous coronary intervention. Post-PCI they will be submitted to the cardiac control unit where they receive the second dose, 6 hours after start of the first dose. The second dose is administered in 30 minutes (infusion rate 8.33 mL/min). At 4 months infarct size is assessed by LGE cardiac magnetic resonance imaging.
Drug: sodium chloride (NaCl)
see description under placebo arm
Other Name: Placebo

Procedure: primary percutaneous coronary intervention
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.
Other Name: PPCI

Other: cardiac magnetic resonance imaging
CMR-imaging will be used for assessment of 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{33}. The full study protocol lasts approximately 45 minutes and includes anatomy and function, LGE and T1-mapping.
Other Name: CMR-imaging




Primary Outcome Measures :
  1. Myocardial infarct size as measured with late gadolinium enhancement cardiac magnetic resonance imaging. [ Time Frame: 4 months after randomization ]
    Primary efficacy parameter


Secondary Outcome Measures :
  1. Left ventricular ejection fraction as assessed by late gadolinium enhancement cardiac magnetic resonance imaging. [ Time Frame: 4 months after randomization ]
    Secondary efficacy parameter

  2. N-terminal prohormone of brain natriuretic peptide (NT pro-BNP) level [ Time Frame: 4 months after randomization ]
    Secondary efficacy parameter

  3. Myocardial haemorrhage as assessed by non-mandatory cardiac magnetic resonance imaging. [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Secondary efficacy parameter

  4. Microvascular obstruction as assessed by non-mandatory cardiac magnetic resonance imaging. [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Secondary efficacy parameter

  5. Myocardial salvage index as assessed by non-mandatory cardiac magnetic resonance imaging. [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Secondary efficacy parameter

  6. Left ventricular ejection fraction as assessed by non-mandatory cardiac magnetic resonance imaging. [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Secondary efficacy parameter

  7. Left ventricular end-diastolic volume as assessed by non-mandatory cardiac magnetic resonance imaging. [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Secondary efficacy parameter

  8. Left ventricular end-systolic volume as assessed by non-mandatory cardiac magnetic resonance imaging. [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Secondary efficacy parameter

  9. Left ventricular mass as assessed by non-mandatory cardiac magnetic resonance imaging. [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Secondary efficacy parameter

  10. Incidence of cardiovascular events [ Time Frame: 4 months after randomization and after 2-year follow-up ]
    Safety parameter. Includes all cause mortality, cardiovascular death, re-infarction, re-intervention both re-PCI and CABG [except for scheduled revascularization based on the index coronary angiography (CAG) to diagnose and treat coronary artery lesions identified during the procedures and heart team discussion, including concomitant treatment of valvular conditions], stroke, internal cardiac defibrillator (ICD) implantation, hospitalization for heart failure or chest pain (defined as an overnight stay, with different dates for admission and discharge) and combined Major adverse cardiac events (MACE) defined as death, re-infarction, any revascularization not planned on index CAG

  11. Enzymatic infarct size as assessed by peak creatinine kinase myocardial band (CK-MB). [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Safety parameter


Other Outcome Measures:
  1. Gender [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Analysis of primary and secondary endpoints according to important risk factors and known medical history collected during routine clinical care for STEMI.

  2. Age in years [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Analysis of primary and secondary endpoints according to important risk factors and known medical history collected during routine clinical care for STEMI.

  3. body mass index in kg/m^2 [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Analysis of primary and secondary endpoints according to important risk factors and known medical history collected during routine clinical care for STEMI.

  4. Location of myocardial infarction (segment) [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Analysis of primary and secondary endpoints according to important risk factors and known medical history collected during routine clinical care for STEMI.

  5. Thrombolysis in myocardial infarction (TIMI) grade flow pre- and post-reperfusion (grade 0-3) [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Analysis of primary and secondary endpoints according to important risk factors and known medical history collected during routine clinical care for STEMI.

  6. Abnormal findings in physical diagnostics [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Analysis of primary and secondary endpoints according to important risk factors and known medical history collected during routine clinical care for STEMI.

  7. Changes in electrocardiographic determinants of myocardial reperfusion [ Time Frame: Up to 4 months follow-up visit. ]
    Changes include incidence of new Q waves, ST-segment resolution, persistent ST-deviation.

  8. Creatine Kinase (IU/L) [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Changes in blood biomarkers

  9. Creatine Kinase myocardial band in international units per litre (IU/L) [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Changes in blood biomarkers

  10. Troponin T in nanogram per millilitre (ng/mL) [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Changes in blood biomarkers

  11. N-terminal prohormone of brain natriuretic peptide (NT-ProBNP) in nanogram per litre (ng/L) [ Time Frame: 0-5 days after randomization (during hospitalization) ]
    Changes in blood biomarkers



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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;
  • Symptoms and/or ST-segment deviation should be present (persisting) at time of arrival in the cath-lab;
  • PPCI is being considered as treatment;
  • Patient is willing to cooperate with follow-up during 2 years.

Exclusion Criteria:

  • Prior MI (STEMI/non-STEMI/acute coronary syndrome (ACS));
  • Need for emergency CABG;
  • Prior coronary revascularization (PCI/CABG);
  • Known cardiomyopathy;
  • History of a malignancy treated with chemo- and/or radiotherapy;
  • Relieve of symptoms and complete ST-segment resolution prior to arrival at the cath-lab;
  • 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 >250kg; known claustrophobia; 3 T magnetic resonance imaging (MRI) incompatible ferromagnetic objects in the body, end-stage renal disease);
  • Pregnancy or breastfeeding women; women of childbearing potential with clinical suspicion of possible pregnancy;
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02899364


Contacts
Contact: Pim van der Harst, Professor 0031503616161 p.van.der.harst@umcg.nl
Contact: Carlijn Maagdenberg, M.D. 0031503616161 c.g.maagdenberg@umcg.nl

Locations
Netherlands
University Medical Centre Groningen Not yet recruiting
Groningen, Netherlands, 9700RB
Principal Investigator: Pim van der Harst, Professor         
Sub-Investigator: Carlijn Maagdenberg, M.D.         
Sponsors and Collaborators
University Medical Center Groningen
Investigators
Principal Investigator: Pim van der Harst, Prof. Dr. University Medical Center Groningen

Publications:

Responsible Party: Carlijn Maagdenberg, M.D., University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT02899364     History of Changes
Other Study ID Numbers: GIPS-IV
2015-001006-34 ( EudraCT Number )
First Posted: September 14, 2016    Key Record Dates
Last Update Posted: September 14, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Carlijn Maagdenberg, University Medical Center Groningen:
Sodium thiosulfate
STEMI
Infarct size
Cardiac magnetic resonance imaging
Hydrogen sulfide

Additional relevant MeSH terms:
Heart Failure
Infarction
Myocardial Infarction
ST Elevation Myocardial Infarction
Heart Diseases
Cardiovascular Diseases
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Vascular Diseases
Sodium thiosulfate
Antidotes
Protective Agents
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Chelating Agents
Sequestering Agents