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

NCT03017963 | Completed Phase 1

• 1 other identifier: SAFE ACS
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to evaluate the safety and maximum tolerable dose (MTD) of sodium thiosulfate in patients presenting with an acute coronary syndrome and treated with primary percutaneous coronary intervention (PPCI) via trans-radial approach in adjunction to standard treatment.

Conditions

Acute Coronary Syndrome

Keywords

acute coronary syndrome; sodium thiosulfate; maximum tolerable dose; dose-limiting toxicity

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  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.

  up to 24 hours or discharge from coronary care unit to the ward/home

Secondary Outcomes (3)

• Severe hypersensitivity/allergic reaction using a binary scale (yes/no)

  up to 24 hours or discharge from coronary care unit to the ward/home

• Nausea/vomiting

  up to 24 hours or discharge from coronary care unit to the ward/home

• effect of STS on oxidative stress markers in blood

  up to 12 hours

Study Arms (1)

dose-escalation cohort

EXPERIMENTAL

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.

Drug: Sodium Thiosulfate Pentahydrate

Interventions

Sodium Thiosulfate Pentahydrate DRUG

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

dose-escalation cohort

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 ACS defined by: chest pain suggestive for myocardial ischemia for at least 30 minutes, the time from onset of the symptoms less than 24 hours before hospital admission, with (STEMI) or without (nSTEMI/uAP) an electrocardiogram (ECG) recording with ST- segment elevation of more than 0.1 millivolt (mV) in 2 or more contiguous leads;
• PCI via trans-radial approach is being considered as treatment;
• Patient is willing to cooperate with the trial during hospitalization

You may not qualify if:

• Known cardiomyopathy or LVEF\<35%;
• History of a malignancy treated with chemo- and/or radiotherapy \< 1 year;
• Systolic blood pressure under 100 mmHg or over 180 mmHg at presentation;
• Cardiogenic shock at presentation
• Sedated and/or intubated patients;
• Pregnant/breastfeeding at time of presentation
• The existence of a condition with a life expectancy of less than 1 year;
• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Centre Groningen

Groningen, 9700RB, Netherlands

Location

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

sodium thiosulfate

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Pim van der Harst, Professor

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: December 24, 2016
• First Posted: January 11, 2017
• Study Start: October 6, 2017
• Primary Completion: March 23, 2018
• Study Completion: March 23, 2018
• Last Updated: April 17, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)