Intravenous unfractionated heparin (UFH) remains the most frequently used anticoagulant for many inpatient indications because of its availability and clinical familiarity. UFH is, however, a high-risk medication with complex, patient-variable pharmacokinetics and pharmacodynamics. These characteristics create a need for reliable laboratory monitoring and frequent titration to maintain therapeutic anticoagulation while limiting bleeding and thrombotic complications.
The conventional method for titration of UFH uses a clot-based assay, the activated partial thromboplastin time (aPTT), typically targeted to approximately one and a half to two and a half times the upper limit of the normal range. An alternative approach uses assays that indirectly measure anti-factor Xa activity (anti-Xa). Prior to the CHAMP trial, these two monitoring strategies had not been compared prospectively in a randomized study within routine clinical practice, so the optimal laboratory test for monitoring and adjusting UFH remained uncertain.
The Comparison of Heparin Assay Monitoring Protocols (CHAMP) Trial was developed to answer this question pragmatically within a learning healthcare infrastructure by directly comparing two established clinical protocols for UFH monitoring used at a single centre.
CHAMP is a single-centre, pragmatic, randomized clinical trial conducted at Vanderbilt University Medical Centre (VUMC). The trial began enrollment on 26 June 2024. The study is embedded into existing clinical workflows for heparin administration with the intent to evaluate the two monitoring protocols under real-world conditions rather than in a tightly controlled efficacy environment.
Admitted adult patients who are initiated on an intravenous UFH protocol as part of routine clinical care are eligible for inclusion under the pragmatic design. Once UFH is started, patients are assigned in a randomized fashion to follow either the aPTT-based protocol or the anti-Xa–based protocol for laboratory monitoring and adjustment of heparin infusion rates.
Because the protocols under study are already in clinical use at the institution and are regarded as clinically equivalent, the trial was implemented with processes that permit integration into standard care and rapid initiation of therapy.
The two arms of the trial use established clinical protocols available at VUMC for titration of intravenous UFH. One arm uses the clot-based aPTT assay, with target ranges defined per the institution’s aPTT-based titration protocol. The comparator arm uses an indirect anti-Xa assay to guide dose adjustments. The CHAMP trial compares these protocols as operationalized in routine practice, including the frequency of laboratory monitoring, decision rules for rate changes, and documentation embedded within clinical workflows.
Specific laboratory thresholds, exact titration rules, and stepwise rate-change algorithms used in each protocol were those already in place at VUMC; these protocol details were not exhaustively described in the source summary.
The prespecified primary outcome for the CHAMP trial is time to reach the therapeutic anticoagulation range by coagulation assay following initiation of intravenous UFH. This outcome assesses how rapidly each monitoring strategy achieves target anticoagulation.
Secondary outcomes include:
These secondary outcomes address both process measures (e.g., monitoring frequency, rate adjustments) and clinical safety and efficacy endpoints (thrombosis and bleeding).
The CHAMP trial received approval from the Vanderbilt Institutional Review Board (IRB #232192) with a waiver of informed consent. The waiver was granted because both monitoring protocols are already used in clinical practice and are considered clinically equivalent, and because prompt initiation of UFH in many clinical scenarios limits the feasibility of obtaining informed consent without affecting care.
Launching and operating the trial relied on partnerships with nursing, pharmacy, and clinical providers to integrate randomised assignment and protocol adherence into routine workflows. Embedding the trial into standard care pathways and using existing protocols facilitated pragmatic implementation.
The CHAMP study was registered on ClinicalTrials.gov with identifier NCT06329921 on 19 March 2024. The first patient was enrolled on 26 June 2024. The study plans to enroll 700 participants, with enrollment expected to occur over approximately two years.
CHAMP is designed to produce the first prospective, randomized, direct comparison of the aPTT and anti-Xa monitoring protocols for intravenous UFH in hospitalized patients. After trial completion and data analysis, the investigators intend to submit the findings to a peer-reviewed journal for broader clinical dissemination. The source summary did not provide additional details on statistical methods, interim analyses, or prespecified subgroup analyses.
By comparing how quickly therapeutic anticoagulation is reached and by measuring monitoring burden and clinical events, the CHAMP trial aims to inform clinical practice on the optimal laboratory approach to guide UFH titration in routine inpatient care.