Clinical trial NCT05740371: Safety of Argatroban Infusion in Conduction Disturbances
Official title: SAICoDis - Safety of Argatroban Infusion in Conduction Disturbances. A Prospective, Open, Multicenter Safety Study to Investigate Conduction Disturbances in Patients Receiving Argatroban Therapy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Stable Coronary Artery Disease (CAD)
Unstable Angina (Troponin Negative)
Lead sponsor: Mitsubishi Tanabe Pharma GmbH
Sponsor class: INDUSTRY
First posted: 2023-02-23
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Difference in QTc Interval Between ECG-2 and ECG-1 (ITT Population)
timeFrame: 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).
measure: Mean Difference in QTc Interval Between ECG-2 and ECG-1 (ITT Population/Subgroup Male or Female)
timeFrame: 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).
measure: Mean Difference in QTc Interval Between ECG-2 and ECG-1 (ITT Population/Centre 01 or Centre 02)
timeFrame: 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 outcomes:
measure: Proportion of Patients With a Prolongation of QTc Interval to >500 ms at ECG-2
timeFrame: ECG-2 immediately after argatroban infusion
Other outcomes:
Locations:
city: Frankfurt am Main
country: Germany
facility: University Hospital Frankfurt
state: Hessen
city: Rotenburg an der Fulda
country: Germany
facility: Herz-Kreislauf-Zentrum Klinikum Hersfeld-Rotenburg
state: Hessen
Study officials:
affiliation: Mitsubishi Tanabe Pharma GmbH
name: Deputy General Manager Scientific Medical Affairs
role: STUDY_DIRECTOR
References: