ClinicalTrials.gov record NCT04745195

Complement Prospective Evaluation of Thrombotic Microangiopathy on Endothelium

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Aug 22, 2026

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

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeObservationalA study in which researchers do not assign participants to a treatment or other intervention. They observe or measure what happens, which may include study visits, tests, questionnaires or a review of medical records.
Age18 years old and older
SexAll
LocationNetherlands
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This is a prospective observational study of adults with thrombotic microangiopathy (TMA), including atypical hemolytic uremic syndrome. Participants are followed for up to 12 months with repeated endothelial-function testing (the HMEC test), monthly ex vivo C5b9 measurements, and routine complement assessments. The study seeks to measure how often complement dysregulation underlies TMA and to evaluate diagnostic and prognostic markers.

What it is studying. The study tests whether a functional endothelial cell-based HMEC test and measurements of ex vivo C5b9 can identify patients whose TMA is driven by complement dysregulation. It also tests how common complement-mediated TMA is along the spectrum of TMA, how the HMEC/C5b9 measures compare with routine complement tests, and whether kidney biopsy features or complement-gene variants relate to kidney and TMA outcomes.

What the researchers hope to learn. Scientific goals: determine the prevalence of complement-mediated TMA; evaluate the diagnostic performance of the HMEC test; describe the monthly dynamics of ex vivo C5b9 on endothelium and compare them with routine complement measures; and assess whether kidney biopsy features and variants in complement genes predict kidney or TMA outcomes.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

Thrombotic microangiopathy (TMA) is a severe and life-threatening condition, often affecting the kidneys and brain. It can occur on the background of various clinical conditions. Dysregulation of the alternative pathway of complement may be the etiological factor and this type of TMA is classified, according to the current nomenclature, as primary atypical hemolytic uremic syndrome (HUS). Half the patients with primary atypical HUS present with rare variants in complement genes, although coexisting conditions are often needed for the TMA to become manifest. In patients with secondary atypical HUS, certain coexisting conditions appear to drive the disease and treatment should target the underlying condition to remit the TMA. Recently, the investigators demonstrated, by using a novel in-house developed functional endothelial cell-based test, that complement dysregulation and overactivation is the dominant cause of disease and its sequelae in a subset of patients with secondary atypical HUS, having impact on treatment and prognosis. The investigators did first prove this concept in patients presenting with TMA and hypertensive emergency. A prospective study is needed to further corroborate these findings along the spectrum of TMA. The investigators hypothesize that their functional endothelial cell-based test, the so-called "HMEC" test, can better categorizes the TMA into different groups with potential therapeutic and prognostic implications. Thus, paving the road to the ultimate goal of precision medicine.

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

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).

Study description and what participation involves

The registry record has no detailed description beyond the summary above.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This is an observational study (no study-assigned treatment). If you join, you will be followed for up to 12 months with visits and testing. Expect monthly tests to measure ex vivo C5b9 formation on the endothelium for up to one year, plus the HMEC endothelial test on the protocol schedule; genetic testing and review of any available kidney biopsy may also occur. You will provide informed consent and permit the study team to collect clinical data and samples during follow-up.

How the study is structured. A prospective observational cohort study. Adults with TMA are enrolled and followed for up to 12 months. The HMEC endothelial test and monthly ex vivo C5b9 measurements are performed and compared with routine complement measures; kidney biopsy features and complement-gene variants are analyzed for diagnostic and prognostic associations.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • This is an observational study, so the study itself gives no treatment. What would taking part involve for me, and would it change my usual care?
  • The listed sites are in Netherlands. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on atypical hemolytic uremic syndrome

Clinical trials13 trials listed for atypical hemolytic uremic syndromeEvery trial the registry lists for atypical hemolytic uremic syndrome, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in atypical hemolytic uremic syndrome researchLatest monthly update: September 2026. Includes: Ravulizumab and labs. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Aug 11, 2021
Primary completion
Dec 31, 2026 (estimated)
Study completion
Dec 31, 2026 (estimated)
Target enrollment
42 participants (estimated)
Last updated on registry
Oct 1, 2025
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Maastricht University Medical Center
Principal investigator
Sjoerd Timmermans, Principal Investigator
Maastricht University Medical Center

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

Terms used on this page · explanations by MedicalUpdates.ai

GFR
A blood-test estimate of how well the kidneys are filtering. Lower numbers mean reduced kidney function; many studies set a minimum value.
biopsy
Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
written informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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