Examining complement-related thrombotic microangiopathy that injures the blood vessel lining

Diagnostic and Risk Criteria for Complement Defects in Thrombotic Microangiopathy and Amplifying Conditions, Such as Severe Hypertension: The COMPETE Study.

This project will test whether a new endothelial cell-based blood test can detect complement overactivation as the cause of thrombotic microangiopathy in adults with acute kidney injury and TMA.

Quick facts

• Study type: Observational
• Enrollment: 42 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Maastricht University Medical Center (other)
• Locations: 1 site (Maastricht, Limburg)
• Trial ID: NCT04745195 on ClinicalTrials.gov

What this trial studies

This is a prospective observational study enrolling adults with acute kidney injury and documented thrombotic microangiopathy. Participants will undergo a novel, in-house endothelial cell-based functional test alongside standard clinical and laboratory data collection to identify complement pathway overactivation. The study includes patients with primary atypical HUS and those with secondary TMA linked to triggers such as hypertensive emergency, pregnancy (including up to 12 weeks postpartum), recent kidney donation/recipient status, or systemic autoimmune disease. All testing and data collection are performed at Maastricht University Medical Center to correlate test results with clinical presentation and outcomes.

Who should consider this trial

Good fit: Adults (≥18 years) with acute kidney injury (eGFR <45 mL/min/1.73 m2) and documented TMA by blood findings or kidney biopsy, and either primary atypical HUS or a coexisting condition linked to complement dysregulation (severe hypertension, pregnancy up to 12 weeks postpartum, recent kidney donor/recipient, or systemic autoimmune disease).

Not a fit: Patients whose TMA is clearly caused by non–complement mechanisms, those without the specified kidney dysfunction or laboratory evidence of TMA, or those unable to attend the Maastricht site are unlikely to benefit from this test.

Why it matters

Potential benefit: If successful, the test could identify patients whose TMA is driven by complement overactivation so they can be considered for targeted complement-directed therapies sooner.

How similar studies have performed: Complement-targeted treatments have proven effective in primary atypical HUS and prior studies link complement dysregulation to TMA, but the specific endothelial cell-based functional assay used here is a newer method with limited prior clinical validation.

Eligibility criteria

Inclusion Criteria:

* Males or females at least 18 years of age;
* Have acute kidney injury, defined as estimated GFR \<45 mL/min/1.73m2;
* Have documented TMA either on peripheral blood, defined as Coombs negative microangiopathic hemolytic anemia (hematocrit \<30%, hemoglobin \<6.5 mmol/L \[\<10 g/dL\], lactate dehydrogenase \>500 U/L, and either schistocytes on peripheral blood smear or undetectable haptoglobin), and platelets \<150,000 per µL, or kidney biopsy;
* Have primary atypical HUS or a coexisting condition linked to complement dysregulation:

  * Hypertensive emergency, defined as SBP/DBP of \>180/120 mmHg and impending organ damage secondary to hypertension (at least one of the following: neurologic disease, hypertensive retinopathy grade III and/or IV, left ventricular hypertrophy); OR
  * Pregnancy, including 12 weeks postpartum; OR
  * Kidney donor recipient; OR
  * Systemic auto-immune disease associated with TMA, including systemic sclerosis, systemic lupus erythematosus, anti-phospholipid syndrome;
* Have the ability to understand the requirements of the study, provide written informed consent, and comply with the study protocol procedures.

Exclusion Criteria:

* Have secondary causes of hypertensive emergency, including renovascular hypertension, Cushing syndrome, aldosteronism, pheochromocytoma, thyroid disease;
* Have a nephropathy not related to thrombosis on kidney biopsy;
* Have ADAMTS13 deficiency, defined as ADAMTS13 activity \<10%;
* Have a positive stool culture for Shiga toxin producing bacteria;
* Have positive serologic test for viral infections, including HIV and CMV;
* Have a history of malignant disease, excluding non-melanoma skin cancer;
* Have a history of bone marrow or solid organ transplantation, excluding kidney transplantation;
* Received at least one of the following agents: chemotherapeutics, sirolimus, anti-VEGF agents;
* Have a history of recent past exposure to illicit drug(s).

Where this trial is running

Maastricht, Limburg

• Maastricht University Medical Center — Maastricht, Limburg, Netherlands (RECRUITING)

Study contacts

• Principal investigator: Pieter van Paassen, MD, PhD — Maastricht University Medical Center
• Study coordinator: Sjoerd A.M.E.G. Timmermans, MD, PhD

Conditions: Thrombotic Microangiopathies, Hemolytic Uremic Syndrome, Atypical, Hemolytic-Uremic Syndrome