Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Ilofotase Alfa in Patients at Risk for Renal Damage Following Open Heart Surgery
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 271
- 试验地点
- 14
- 主要终点
- Serum Creatinine Level Ratio
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- 干预性
- 分配方式
- 随机
- 干预模型
- 平行分组
- 主要目的
- 治疗
- 盲法
- 三盲 (受试者、研究者、结局评估者)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- Age ≥18 years
- 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
- Screening eGFR ≥25 mL/min/1.73m2 and ≤65 mL/min/1.73m2
- 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.
- 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
排除标准
- 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
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Ilofotase alfa
干预措施: Ilofotase alfa (Drug)
方案终点
主要结局
Serum Creatinine Level Ratio
时间窗: From Baseline (Day -1/1) to Day 5
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.
Assessment of serum creatinine values
时间窗: From Baseline to Day 5
Ratio between the highest value postsurgery (post-surgery Day 1 and Days 2, 3, 4, and 5) and the pre-surgery baseline value for serum creatinine
次要结局
- Assessment of Major Adverse Kidney Events (MAKE) 60(60 days)
- (Serious) Adverse Events up to Day28(Day1 to Day28)
- Assessment of major adverse kidney events (MAKE) 60(Daily post-surgery through Day 5)
- Assessment of adverse event (AE) and serious adverse event (SAE) occurrence(From Day -1 to Day 28)
试验结果
结果已于 2026-09-29 在 ClinicalTrials.gov 公示。 在 ClinicalTrials.gov 查看
受试者流程
入组 244 人 · 完成 193 人
主要终点
Serum Creatinine Level Ratio
Ratio · Standard Deviation · 时间窗: From Baseline (Day -1/1) to Day 5
| Placebo （n=95） | Ilofotase Alfa （n=109） |
|---|---|
| 1.27 (0.502) | 1.21 (0.422) |
For the efficacy endpoints the study population has been used which did receive two injections of the investigational medicinal product (Full Analysis Set).
Difference in LS means -0.066 · 95% 置信区间 -0.194–0.061 · p = 0.3059 · ANCOVA
ANCOVA of the sCreat ratio, with pre-surgery sCreat baseline value, eGFR category (stratum) and type of surgery (stratum) as covariates.
其他终点（5）
Assessment of Major Adverse Kidney Events (MAKE) 60
Participants · 时间窗: 60 days
| 分类 | Placebo （n=95） | Ilofotase Alfa （n=109） |
|---|---|---|
| MAKE 60 — MAKE 60 (imputed for missing data) | 15 | 17 |
| Death up to and including D61 — MAKE 60 (imputed for missing data) | 2 | 2 |
| Received any RRT post-surgery up to and including D61 — MAKE 60 (imputed for missing data) | 6 | 4 |
| Decrease eGFR of ≤25% at D61 compared to baseline — MAKE 60 (imputed for missing data) | 8 | 12 |
For the efficacy endpoints the study population has been used which did receive two injections of the investigational medicinal product (Full Analysis Set).
Odds Ratio (OR) 0.936 · 95% 置信区间 0.416–2.105 · p = 0.8726 · Regression, Logistic
The statistical analysis of MAKE60 is based on imputed values (multiple imputation), for patients with missing information at Day 61.
Logistic regression using pre-operative baseline sCreat value and the stratification factors as covariates.
Cumulative AKI Severity (Area Under the Curve)
AKI severity score * days · Standard Deviation · 时间窗: From Day 1 to Day 5
| Placebo （n=95） | Ilofotase Alfa （n=109） |
|---|---|
| 0.99 (1.87) | 0.72 (1.53) |
For the efficacy endpoints the study population has been used which did receive two injections of the investigational medicinal product (Full Analysis Set).
Test statistic Van-Elteren test 1.181 · p = 0.2377 · Two-sided
Number of Participants With KDIGO AKI
Participants · 时间窗: From Day 1 to Day 5
| Placebo （n=95） | Ilofotase Alfa （n=109） |
|---|---|
| 34 | 34 |
For the efficacy endpoints the study population has been used which did receive two injections of the investigational medicinal product (Full Analysis Set).
Odds Ratio (OR) 0.714 · 95% 置信区间 0.389–1.309 · p = 0.2757 · Regression, Logistic
Logistic regression using pre-operative baseline sCreat value and the stratification factors as covariates.
Assessment of Length of Stay in the Intensive Care Unit
days · Standard Deviation · 时间窗: From Baseline to Day 28
| Placebo （n=94） | Ilofotase Alfa （n=109） |
|---|---|
| 5.4 (9.3) | 4.5 (6.0) |
For the efficacy endpoints the study population has been used which did receive two injections of the investigational medicinal product (Full Analysis Set).
(Serious) Adverse Events up to Day28
Participants · 时间窗: Day1 to Day28
| 分类 | Placebo （n=108） | Ilofotase Alfa （n=112） |
|---|---|---|
| Adverse events up to Day28 | 71 | 69 |
| Serious adverse events up to Day28 | 22 | 22 |
For the safety endpoints the study population has been used which did receive at least one injections of the investigational medicinal product
安全性
| 组别 | 严重不良事件 | 死亡 |
|---|---|---|
| Placebo | 23 / 108 | 2 / 108 |
| Ilofotase Alfa | 23 / 112 | 2 / 112 |
最常见的严重不良事件（人数）
| 事件 | Placebo | Ilofotase Alfa |
|---|---|---|
| Acute kidney injury | 3 / 108 | 1 / 112 |
| Atrial fibrillation | 0 / 108 | 2 / 112 |
| Atrioventricular block complete | 2 / 108 | 2 / 112 |
| Pericardial effusion | 0 / 108 | 2 / 112 |
| Urinary tract infection | 2 / 108 | 0 / 112 |
| anaemia | 0 / 108 | 1 / 112 |
| Acute coronary syndrome | 1 / 108 | 0 / 112 |
| Arrhythmia | 1 / 108 | 0 / 112 |
| Atrial thrombosis | 1 / 108 | 0 / 112 |
| Bradycardia | 1 / 108 | 0 / 112 |
数值为申办方在 ClinicalTrials.gov 公示的原始数据，未经重新计算；括号内为公示的离散度（如 95% 置信区间）。
相关文献
- 相关文献（PubMed 关联）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. PubMed 42766022
- 相关文献（PubMed 关联）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. PubMed 40152923
研究者
研究点 (14)
标识符
- NCT 编号
- NCT06168799
- 其他研究编号
- AP-recAP-CSA-RD-02-01, WHO Universal Trial Number, EU Clinical Trial Number
日期
- 首次提交
- (2年前)
- 首次发布
- (2年前)
- 主要完成日期
- (12个月前)
- 研究完成日期
- (10个月前)
- 最近核实
- (29天前)
- 最近更新
- (昨天)
监管与共享
- FDA 监管药物
- 是
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 否
- 是否有结果
- 是