Ilofotase Alfa per la prevenzione del danno renale dopo un intervento di cardiochirurgia
Studio in doppio cieco, randomizzato, controllato con placebo per valutare l'efficacia e la sicurezza di Ilofotase Alfa in pazienti a rischio di danno renale dopo intervento chirurgico a cuore aperto
The aim of this clinical trial is to evaluate the efficacy and safety of two intravenous administrations of ilofotase alfa in patients at risk for renal damage following open heart surgery.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, 2-arm parallel group design trial in patients at risk for renal damage following open heart surgery. After screening and baseline assessments, eligible patients will be randomized 1:1 to either 2 doses of 128 mg ilofotase alfa, or 2 doses of placebo control. Randomization will be stratified by baseline eGFR and type of surgery. The patient will be treated with the investigational product (ilofotase alfa or placebo) at the same day before and after the surgery (Day 1). Follow-up clinic visits will be performed daily up to Day 5 for efficacy, safety, and pharmocokinetics assessments. A safety follow-up can be performed by telephone at Day 28. At Day 61, an end of trial visit will be done at site for efficacy, safety, and anti-drug antibodies assessments.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Genk, Belgio
- Ziekenhuis Oost Limburg
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Ghent, Belgio
- Universitair Ziekenhuis Gent
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Roeselare, Belgio
- Algemeen Ziekenhuis Delta
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Essen, Germania
- Universität Duisburg-Essen, Klinik für Thorax- und Kardiovaskuläre Chirurgie
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Munich, Germania
- Deutsches Herzzentrum Muenchen Des Freistaates Bayern Klinik An Der Technischen Universitaet Muenchen
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Münster, Germania
- Westfaelische Wilhelms-Universitaet Muenster
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Tübingen, Germania
- Universitätsklinikum für Anästhesiologie und Intensivmedizin, Universitätsklinikum Tübingen
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Amsterdam, Olanda
- Academisch Medisch Centrum Amsterdam
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Nijmegen, Olanda
- Stichting Radboud University Medical Center
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Rotterdam, Olanda
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
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London, Regno Unito
- Guy's and St Thomas' NHS Foundation Trust
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Bern, Svizzera
- Universitätsspital Bern Universitätsklinik für Herzchirurgie
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Lausanne, Svizzera
- Centre hospitalier universitaire vaudois (CHUV)
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
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Age ≥18 years
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Planned for one of the following types of open chest cardiovascular surgery with the use of cardiopulmonary bypass pump (CPB):
- 1. combined valve and CABG surgery; 2. aortic valve plus aortic root and/or ascending aorta (excluding aortic arch)
- CABG with 3 or more distal anastomoses
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Screening eGFR ≥25 mL/min/1.73m2 and ≤65 mL/min/1.73m2
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Female patients of childbearing potential agreeing to use effective contraception within IP treatment and 14 days thereafter
Post-menopausal females do not require contraception during the trial.
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Male patients agreeing to refrain from donating sperm, use a male condom when having sexual intercourse and in case their partner is of childbearing potential they must agree to use adequate and effective contraception method (see inclusion criterion 4) within IP treatment and 14 days thereafter
The five most important Exclusion Criteria:
- Body weight ≤55 kg
- Known or suspected glomerulonephritis (other than diabetic kidney disease) or other systemic vasculitis
- Confirmed or treated endocarditis requiring antimicrobial or antiviral treatment within 30 days prior to surgery or other current active infection requiring antimicrobial or antiviral treatment within 14 days prior to surgery
- Known chronic liver disorder with Child-Pugh C classification
- Current planned (or scheduled) surgical intervention under conditions of circulatory arrest, including planned deep hypothermic circulatory arrest
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Comparatore placebo: Placebo
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After dilution of the concentrate, the investigational medicinal product will be administered by intravenous infusion for 1 hour at the same day before and after the surgery (Day 1) |
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Sperimentale: Ilofotase alfa
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After dilution of the concentrate, the investigational medicinal product will be administered by intravenous infusion for 1 hour at the same day before and after the surgery (Day 1) |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Serum Creatinine Level Ratio
Lasso di tempo: From Baseline (Day -1/1) to Day 5
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Ratio between the highest serum creatinine value post-surgery (post-surgery Day 1 and Days 2, 3, 4, and 5) and baseline serum creatinine (pre-surgery, Day -1/Day 1). The values at post-surgery Day 1 and Days 2, 3, 4, and 5 compared to the value at baseline (Day -1/Day 1) are used to calculate the serum creatinine ratio. The reported means and standard deviations are based on patient-level ratios and include observed and imputed values. |
From Baseline (Day -1/1) to Day 5
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Assessment of Major Adverse Kidney Events (MAKE) 60
Lasso di tempo: 60 days
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Major adverse kidney events (MAKE) 60, defined as died up to and including Day 61, have received or are receiving new renal replacement therapy (RRT) up to and including Day 61, or have a decrease in estimated glomerular filtration rate (eGFR) ≥25% on Day 61 compared to the pre-surgery baseline eGFR reference value. With Day 1 being the day of surgery. |
60 days
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(Serious) Adverse Events up to Day28
Lasso di tempo: Day1 to Day28
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All AEs that occured up to and including Day 28 or patient's trial completion, whichever occurs first. |
Day1 to Day28
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Altre misure di risultato
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Cumulative AKI Severity (Area Under the Curve)
Lasso di tempo: From Day 1 to Day 5
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Area under the curve of daily AKI severity stage/grade (0-3) from Day 1 to Day 5; higher values indicate greater cumulative AKI severity |
From Day 1 to Day 5
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Number of Participants With KDIGO AKI
Lasso di tempo: From Day 1 to Day 5
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KDIGO AKI stage was measured daily from Day 1 to Day 5 after surgery. A participant was counted as 'participant with KDIGO AKI', if the AKI stage was at least one day >0 from Day 1 to Day 5 after surgery. |
From Day 1 to Day 5
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Assessment of Length of Stay in the Intensive Care Unit
Lasso di tempo: From Baseline to Day 28
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Length of stay in the intensive care unit (ICU) in days after the initial surgery |
From Baseline to Day 28
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Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Pickkers, Prof, MD, PhD, Radboud University Medical Center
Pubblicazioni e link utili
Pubblicazioni generali
- Tellez Garcia JM, Steenvoorden T, Bemelman F, Hilhorst M, Tammaro A, Vogt L. Purinoreceptor P2X7 in Extracellular ATP-Mediated Inflammation through the Spectrum of Kidney Diseases and Kidney Transplantation. J Am Soc Nephrol. 2025 Mar 28;36(9):1823-1843. doi: 10.1681/ASN.0000000711.
- Mourisse L, Ostermann M, Thiessen S, Dumoulin A, Vlaar APJ, Hoste E, Mosbahi S, Schneider A, Zarbock A, Boehm J, Rosenberger P, Thielmann M, Dubois E, Powell-Tuck J, Baig K, Renette W, Meex I, Klop-Rhiel M, Opschoor K, Vandenberghe W, Siepe M, Strauss C, Wirth F, Winkel M, Hof L, Kraan M, Bernholz J, Pickkers P; study team. A multicenter randomized, double-blinded placebo-controlled phase 2 trial to evaluate safety and efficacy of ilofotase alfa in patients at risk for kidney injury following open heart surgery. Intensive Care Med. 2026 Sep 21. doi: 10.1007/s00134-026-08596-y. Online ahead of print.
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Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Altri numeri di identificazione dello studio
- AP-recAP-CSA-RD-02-01
- WHO Universal Trial Number (Identificatore di registro: U1111-1295-0827)
- EU Clinical Trial Number (Identificatore di registro: 2023-505859-45)
Piano per i dati dei singoli partecipanti (IPD)
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