Safety of Argatroban Infusion in Conduction Disturbances (SAICoDis)

SAICoDis - Safety of Argatroban Infusion in Conduction Disturbances. A Prospective, Open, Multicenter Safety Study to Investigate Conduction Disturbances in Patients Receiving Argatroban Therapy.

To determine change of QTc interval during intravenous argatroban infusion in patients undergoing percutaneous coronary intervention (PCI)

Study Overview

• Status: Completed
• Conditions: Stable Coronary Artery Disease (CAD); Unstable Angina (Troponin Negative)
• Intervention / Treatment: Drug: Argatroban

Detailed Description

Primary objective:

To determine change of corrected QT interval (QTc) during intravenous argatroban infusion in patients undergoing percutaneous coronary intervention (PCI).

Secondary objectives:

• Determination of the QTc interval after sufficient wash-out period by ECG-3 which needed to be performed > 8 but ≤ 28 hours after termination of prolonged argatroban infusion.
• Investigation of dependence of QTc interval on gender and applied doses.
• Determination of coagulation status during argatroban therapy.
• Assessment of safety-related events within the scope of anticoagulation with argatroban, for example bleeding events or thromboembolic events.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • University Hospital Frankfurt
    • Rotenburg an der Fulda, Hesse, Germany, 36199
      • Herz-Kreislauf-Zentrum Klinikum Hersfeld-Rotenburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of stable CAD or unstable angina (troponin negative, i.e. within the normal range for the study site) with low to moderate anatomic risk.
• Patient required elective percutaneous coronary angioplasty or stent insertion with an approved device in one or more de novo-treated or re-stenotic lesions in native vessels.
• Patient was on adequate platelet inhibition therapy after having received a loading dose with ASA and clopidogrel before start of intervention (this additional inclusion criterion was introduced with study protocol version 1.6, dated 14.12.2018)
• Willingness to give written informed consent, written consent for data protection (legal requirement in Germany "datenschutzrechtliche Einwilligung") and willingness to participate and to comply with the requirements of the study protocol.
• The patient (female/male) was at least 18 years of age.
• Baseline ECG without changes that impair assessment of QTc interval.

Exclusion Criteria:

• Patient was indicated for highly complex 3-vessel intervention.
• The female patient was pregnant (exclusion by routine urine test) or was nursing during therapy period.
• Patients who were currently participating in another clinical trial or patients who participated in another clinical trial during the last 3 months prior to study start (date of treatment visit).
• History of drug, alcohol or chemical abuse within 6 months prior to study start.
• Planned surgical intervention other than study procedure within 7 days after study start.
• Any condition, which contraindicated the use of argatroban, or endangered the patient if he/she participated in this study.

Factors influencing QTc interval:

• Marked baseline prolongation of QTc interval (repeated demonstration of a QTc interval > 450 ms at baseline ECG).
• A history of risk factors of Torsade de pointes (e.g. heart failure, hypokalemia, family history of Long QT Syndrome).
• Known intraventricular conduction disturbance.
• Bradycardia: heart rate < 45 min-1.
• Electrolyte level outside normal range (according to laboratory's reference values).
• The use of concomitant medications that interfered with the QTc interval.
• Intake of digitalis within the last 2 weeks before study start.
• Acute myocardial infarction or troponin-positive unstable angina.

Factors inhibiting use of argatroban in this study:

• Intolerance to ingredients of Argatra® (sorbitol).
• Known cirrhosis, hepatitis, clinically significant hepatic disorder at study start and/or history of clinically relevant hepatic disorder.
• Current hepatic disorder indicated by laboratory liver profile at screening: Bilirubin, AST/SGOT, ALT/SGPT, gammaGT > 3.0 times upper limit of the normal (ULN).
• Renal insufficiency indicated by laboratory renal profile at study start: GFR < 35 ml/min.
• Uncontrolled hypertension (defined as blood pressure >180/120 mmHg).
• If any form of heparin was taken prior to study start and aPTT ≥ 35 s.
• Intake of direct oral anticoagulants (DOAC) within 1 month prior to study start.
• If anticoagulants of type of vitamin K antagonists (VKA) were taken prior to study start and INR >1.2.
• Platelet count <125 x 109/l.
• Documented coagulation disorder or bleeding diathesis.
• Uncontrolled haemorrhage within the past 3 months.
• Uncontrolled peptic ulcer disease or gastrointestinal bleeding within the past 3 months.
• Cerebral aneurysm.
• Haemorrhagic stroke or ischaemic stroke in the past 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Argatroban

Drug: Argatroban; Patients received an intravenous (i.v.) bolus of 300 μg/kg argatroban administered over a span of 3 to 5 minutes followed by the i.v. infusion of argatroban at 20 μg/kg/min until the end of the procedure. ACT was checked 5 minutes after bolus dose. If ACT remained below the target of 300 s, the patient received an additional i.v. bolus injection of 150 μg/kg and the infusion dose was raised up to 30 μg/kg/min. In cases ACT > 450 s, the infusion was reduced to 15 μg/kg/min and the value was checked again after 5 minutes. As soon as the target ACT (between 300 s and 450 s) was reached, infusion dose remained unchanged during the PCI procedure. Depending on clinical relevancy further ACT assessments were possible.; Other Names: Arganova; Argatra; Novastan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Difference in QTc Interval Between ECG-2 and ECG-1 (ITT Population)	It was investigated if a mean QTc prolongation of more than 10 ms occurred between ECG-2 and ECG-1	ECG-2 was recorded immediately after cardiac intervention when patient was fully anticoagulated with argatroban and ECG-1 was recorded at baseline prior to first bolus dose of argatroban (argatroban-free status).
Mean Difference in QTc Interval Between ECG-2 and ECG-1 (ITT Population/Subgroup Male or Female)	It was investigated if a mean QTc prolongation of more than 10 ms occurred between ECG-2 and ECG-1	ECG-2 was recorded immediately after cardiac intervention when patient was fully anticoagulated with argatroban and ECG-1 was recorded at baseline prior to first bolus dose of argatroban (argatroban-free status).
Mean Difference in QTc Interval Between ECG-2 and ECG-1 (ITT Population/Centre 01 or Centre 02)	It was investigated if a mean QTc prolongation of more than 10 ms occurred between ECG-2 and ECG-1	ECG-2 was recorded immediately after cardiac intervention when patient was fully anticoagulated with argatroban and ECG-1 was recorded at baseline prior to first bolus dose of argatroban (argatroban-free status).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With a Prolongation of QTc Interval to >500 ms at ECG-2	Number of patients of ITT population exhibiting QTc interval of > 500 ms	ECG-2 immediately after argatroban infusion

Collaborators and Investigators

• Sponsor: Tanabe Pharma GmbH
• Investigators: Study Director: Deputy General Manager Scientific Medical Affairs, Tanabe Pharma GmbH

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2017
• Primary Completion (Actual): May 6, 2021
• Study Completion (Actual): May 6, 2021

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: February 13, 2023
• First Posted (Actual): February 23, 2023

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Myocardial Ischemia; Chest Pain; Angina Pectoris; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Angina, Unstable; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; argatroban
• Other Study ID Numbers: ARG-E08; 2016-003521-42 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No