Ilofotase Alfa til forebyggelse af nyreskade efter hjertekirurgi
Dobbeltblind, randomiseret, placebokontrolleret undersøgelse for at evaluere effektiviteten og sikkerheden af Ilofotase Alfa hos patienter med risiko for nyreskade efter åben hjertekirurgi
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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Genk, Belgien
- Ziekenhuis Oost Limburg
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Ghent, Belgien
- Universitair Ziekenhuis Gent
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Roeselare, Belgien
- Algemeen Ziekenhuis Delta
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London, Det Forenede Kongerige
- Guy's and St Thomas' NHS Foundation Trust
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Amsterdam, Holland
- Academisch Medisch Centrum Amsterdam
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Nijmegen, Holland
- Stichting Radboud University Medical Center
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Rotterdam, Holland
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
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Bern, Schweiz
- Universitätsspital Bern Universitätsklinik für Herzchirurgie
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Lausanne, Schweiz
- Centre hospitalier universitaire vaudois (CHUV)
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Essen, Tyskland
- Universität Duisburg-Essen, Klinik für Thorax- und Kardiovaskuläre Chirurgie
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Munich, Tyskland
- Deutsches Herzzentrum Muenchen Des Freistaates Bayern Klinik An Der Technischen Universitaet Muenchen
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Münster, Tyskland
- Westfaelische Wilhelms-Universitaet Muenster
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Tübingen, Tyskland
- Universitätsklinikum für Anästhesiologie und Intensivmedizin, Universitätsklinikum Tübingen
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Tredobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Placebo komparator: 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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Eksperimentel: 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) |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Serum Creatinine Level Ratio
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Assessment of Major Adverse Kidney Events (MAKE) 60
Tidsramme: 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
Tidsramme: 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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Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Cumulative AKI Severity (Area Under the Curve)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Pickkers, Prof, MD, PhD, Radboud University Medical Center
Publikationer og nyttige links
Generelle publikationer
- 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.
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Andre undersøgelses-id-numre
- AP-recAP-CSA-RD-02-01
- WHO Universal Trial Number (Registry Identifier: U1111-1295-0827)
- EU Clinical Trial Number (Registry Identifier: 2023-505859-45)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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