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Safety and Efficacy of Eculizumab in High-risk TA-TMA

RecruitingPhase 2Ages 18 Years - anyAllFirst Affiliated Hospital of Zhejiang University
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In plain words

What the trial is, and whether it could suit you

High-risk, complement-mediated, untreated transplant-associated thrombotic microangiopathy (hrTA-TMA) carries a very poor prognosis due to multiple organ dysfunction syndrome (MODS). The complement C5 inhibitor eculizumab has shown promising efficacy in children with hrTA-TMA, but has not been prospectively studied in adult allogeneic hematopoietic stem cell transplantation (HSCT) recipients. The investigators plan to conduct the first multicenter prospective study in adults to evaluate eculizumab as an early targeted intervention for hrTA-TMA. The investigators hypothesize that eculizumab will more than double the survival rate of hrTA-TMA in adult HSCT recipients compared with untreated hrTA-TMA patients from our previous study, who will serve as historical controls. Inclusion criteria are a confirmed diagnosis of TA-TMA with at least one of the following hrTA-TMA features: random urin

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📋 Eligibility rules (as published)
Inclusion Criteria: * Age ≥18 years. * Patients who have undergone hematopoietic stem cell transplantation for any indication within 12 months prior to enrollment. * Meet the diagnostic criteria for TA-TMA within ≤14 days prior to enrollment (at least 4 of the following 7 criteria present simultaneously):① Lactate dehydrogenase (LDH) above the age-adjusted upper limit of normal;② Presence of schistocytes on peripheral blood smear;③ New-onset thrombocytopenia or requirement for platelet transfusions;④ New-onset anemia or requirement for red blood cell transfusions;⑤ Hypertension;⑥ Random urine protein-to-creatinine ratio (rUPCR) ≥1 mg/mg;⑦ Elevated plasma soluble C5b-9 (sC5b-9) level (≥244 ng/mL). * Meet the criteria for high-risk TA-TMA (presence of any of the following):① Proteinuria (rUPCR ≥2 mg/mg);②Multiple organ dysfunction syndrome (MODS);③ Elevated IL-10 (≥2× upper limit of normal \[ULN\]). * Meet the following condition: TA-TMA has not resolved after ≥72 hours of management of triggering factors/conditions, including: ① Discontinuation or dose reduction of inciting medications (e.g., calcineurin inhibitors, CNI); ② Treatment of any underlying infection; ③ Treatment of underlying acute graft-versus-host disease (aGVHD). * Provide written informed consent. Exclusion Criteria: * Known hypersensitivity to eculizumab. * Uncontrolled severe infection (including meningococcal infection). * Prior treatment with complement inhibitors. * Known hereditary or acquired ADAMTS13 deficiency (activity \<10%). * Disseminated intravascular coagulation (DIC). * Respiratory failure (any cause) requiring mechanical ventilation, occurring within 72 hours prior to enrollment. * Acute and/or chronic heart failure with ejection fraction ≤40%. * Expected survival \<48 hours. * Any subject who, in the investigator's opinion, is not suitable for participation in this study.
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What it tests

  • Eculizumab
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Where

8 sites
Xiangya Hospital of Central South University
Changsha, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, China
The First Affiliated Hospital, Zhejiang University School of Medicine.
Hangzhou, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, China
Jinhua Central Hospital
Jinhua, China
The Affiliated People's Hospital of Ningbo University
Ningbo, China
The First Affiliated Hospital of Ningbo University
Ningbo, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, China
🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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