NCT Number: NCT07418099
Prolonged activated partial thromboplastin time (APTT) is a frequent laboratory finding that may reflect a broad spectrum of underlying conditions, ranging from benign laboratory abnormalities to clinically relevant hemostatic disorders. Clot waveform analysis (CWA), automatically generated during routine APTT testing by optical coagulation analyzers, provides additional quantitative and qualitative information on clot formation dynamics.
The APTTO model is a previously developed two-step predictive algorithm based on CWA features designed to estimate the probability of a pathological cause of prolonged APTT and to differentiate lupus anticoagulant from intrinsic pathway factor deficiency or von Willebrand disease. Internal validation has demonstrated good discrimination and calibration.
This multicenter observational study aims to perform an external validation of the APTTO model in independent patient cohorts, assessing its discrimination, calibration, and decision-analytic performance without model updating.
Interested in participating?
Request InfoAll sexes
Observational
Hospital Universitario Severo Ochoa, Leganés, Madrid, Spain
This multicenter observational cohort study is designed to externally validate the APTTO predictive model in patients with prolonged APTT and normal prothrombin time evaluated in routine clinical practice across multiple hospitals.
All laboratory data, including CWA parameters and waveform morphology, are generated as part of standard diagnostic workflows. No additional blood sampling, laboratory testing, or modifications to clinical management are introduced for research purposes.
The study focuses on evaluating model performance in independent cohorts by applying the original APTTO model coefficients and predefined cut-offs without recalibration or re-estimation. Model discrimination, calibration, and decision-analytic measures will be assessed. Secondary analyses will explore model performance across predefined subgroups and analytical robustness.
This study adheres to the TRIPOD statement for validation of prediction models.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
2- Inadequate preanalytical conditions, defined as non-compliance with the study SOP, including but not limited to:
5- Patients with missing essential clinical or laboratory data required for application of the APTTO models.
Application of the APTTO predictive models (APTTO1 and APTTO2) to clot waveform analysis parameters generated during routine activated partial thromboplastin time testing, for research purposes only. The model output does not influence clinical management or surgical decision-making during the study.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
Discrimination of the APTTO1 and APTTO2 models for identifying the cause of prolonged activated partial thromboplastin time (APTT), assessed by the area under the receiver operating characteristic curve (AUC) in an independent multicenter cohort.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
Calibration-in-the-large of the APTTO1 and APTTO2 models assessing agreement between predicted and observed probabilities in an independent multicenter cohort.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
Calibration slope of the APTTO1 and APTTO2 models, evaluating the relationship between predicted and observed risk across the probability spectrum.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
Overall prediction error of the APTTO1 and APTTO2 models, assessed using the Brier score.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
Net clinical benefit of the APTTO models compared with investigate-all and investigate-none strategies, assessed by decision curve analysis across clinically plausible threshold probabilities.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
Sensitivity, specificity, positive predictive value, and negative predictive value of predefined APTTO cut-offs for identifying pathological causes of prolonged APTT.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
Agreement between local investigators and central reader (blinded to clinical data) for qualitative clot waveform morphology classification, assessed using Cohen´s kappa or Fleiss´kappa statistics, as appropriate.
Time frame: Baseline (model-based estimation using timing data from index APTT laboratory assessment through surgical clearance)
Estimated potential reduction in time to surgical cleareance and avoidance of additional etiologic testing based on application of the APTTO algorithm.
Time frame: During the preoperative evaluation period
Assessment of the association between clot waveform morphology, particularly strictly normal waveform patterns, and the severity of intrinsic pathway factor deficiencies in patients with prolonged activated partial thromboplastin time (APTT). This analysis aims to determine whether a normal waveform is associated with higher residual factor levels and a lower likelihood of clinically relevant deficiency.
During the course of the study, additional exploratory objectives were incorporated to further investigate the clinical and physiological implications of clot waveform analysis. In particular, the relationship between strictly normal waveform morphology and the severity of factor deficiency will be evaluated prospectively in the remaining study cohort.
Time frame: During the preoperative evaluation period and up to 30 days after surgery.
Evaluation of the clinical impact of implementing a clot waveform analysis-based diagnostic strategy (APTTO) in the preoperative management of prolonged activated partial thromboplastin time (APTT). This analysis will compare patients managed before and after implementation of APTTO at the development center, time to surgical clearance, and perioperative outcomes.
This objective was incorporated during the course of the study to further assess the clinical implications of APTTO in routine practice and will be evaluated prospectively in the remaining study cohort.
Contact information is provided by the study sponsor or research team.
Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
Other
Multicenter External Validation of the APTTO Predictive Model Based on Clot Waveform Analysis for the Assessment of Prolonged Activated Partial Thromboplastin Time
Acronym: APTTO-EXT
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
Published trials that share one or more normalized conditions with this study.
NCT04517461
Anticoagulants and Bleeding Disorders, Avitaminosis
Lund, Skåne County, Sweden
View Trial DetailsNCT04076605
Bleeding, Blood Coagulation Disorders
Charlottesville, Virginia, United States
View Trial DetailsNCT05806346
Blood Coagulation Disorders, Cardiovascular Diseases
Seoul, South Korea
View Trial DetailsNCT05591014
Blood Coagulation Disorders, Coagulation Disorder, Blood
Salt Lake City, Utah, United States
View Trial Details