Chronic Thromboembolic Pulmonary Hypertension (CTEPH)NCT07902011
CTEPH Differential Diagnosis Assisted by Enhanced Large Language Model Support
A study testing Locked CTEPH-LLM Diagnostic Decision Support in people with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Acute Pulmonary Embolism (PE), run by China-Japan Friendship Hospital at 1 site in China.
Trial summary
This randomized controlled trial aims to evaluate whether a locked large language model (LLM)-based clinical decision support system improves the differential diagnosis of pulmonary artery filling defects among physicians who do not specialize in pulmonary vascular diseases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Thromboembolic Pulmonary Hypertension (CTEPH), Acute Pulmonary Embolism (PE), Pulmonary Artery Sarcoma
- What is being tested?
- Locked CTEPH-LLM Diagnostic Decision Support
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2026to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Holds a valid physician qualification, or is enrolled in a standardized residency training program and is permitted to participate in clinical care under supervision.
- Has not previously reviewed the validation cases or their final diagnoses.
- Is willing to participate and provides informed consent.
- Is able to use the standardized study platform and complete two formal case-reading sessions covering all 30 cases.
Who cannot join
- Has a specialist professional background in pulmonary vascular disease, pulmonary hypertension, or thoracic imaging.
- Participated in validation-case selection, reference-standard confirmation, model development, prompt optimization, or review of locked model outputs.
- Is unable to use the standardized platform or to comply with independent case interpretation and the prohibition on external generative AI tools.
- Has another circumstance that, in the investigator's judgment, could materially compromise independent case interpretation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Large Language Model-Assisted Differential Diagnosis of Pulmonary Artery Filling Defects: A Stratified Randomized Controlled Trial
This randomized controlled trial aims to evaluate whether a locked large language model (LLM)-based clinical decision support system improves the differential diagnosis of pulmonary artery filling defects among physicians who do not specialize in pulmonary vascular diseases. Participants will evaluate 30 de-identified clinical cases involving chronic thromboembolic pulmonary hypertension (CTEPH), acute pulmonary embolism (PE), and pulmonary artery sarcoma (PAS), with or without LLM assistance. The primary outcome is sensitivity for identifying CTEPH, while secondary outcomes include overall diagnostic accuracy, time to diagnosis, appropriateness of referral recommendations, and AI-related diagnostic errors.
Read the detailed description
Pulmonary artery filling defects can result from several conditions, including chronic thromboembolic pulmonary hypertension (CTEPH), acute pulmonary embolism (PE), and pulmonary artery sarcoma (PAS). Distinguishing these conditions can be challenging for physicians who do not specialize in pulmonary vascular diseases. This prospective randomized controlled trial aims to assess whether a clinical decision support system using a locked large language model (LLM) can improve diagnostic performance and reduce diagnostic errors. The study will enroll up to 66 physicians, with a target of 60 participants completing the trial. After providing informed consent and completing a baseline assessment, participants will be stratified by professional seniority and randomly assigned in a 1:1 ratio to either an LLM assisted group or a control group. Randomization will be performed using a computer generated sequence, with allocation concealed until baseline assessments are completed. All participants will independently evaluate the same 30 deidentified clinical cases, including 10 cases each of CTEPH, acute PE, and PAS. The diagnoses will be confirmed by relevant specialists using established diagnostic criteria. These cases will not have been used for model development or optimization. Each participant will complete two sessions of 15 cases, separated by 3 to 7 days, with case order randomized for each participant. Clinical information will be presented in four stages: clinical history and physical examination, laboratory findings, echocardiography, and computed tomography pulmonary angiography (CTPA). Participants will record their diagnosis at each stage before receiving additional information. The control group will make diagnostic decisions based on the available clinical information, while the LLM assisted group will also receive the model's most likely diagnosis, supporting and opposing evidence, and referral recommendations. The model version, prompts, parameters, and case specific outputs will be fixed before randomization and remain unchanged throughout the study. The primary outcome is sensitivity for identifying CTEPH after all four stages. Secondary outcomes include diagnostic accuracy across all three conditions, diagnostic performance at each stage, time to diagnosis, appropriateness of referral recommendations, and errors associated with reliance on incorrect LLM recommendations. Analyses will follow the intention to treat principle. Mixed effects logistic regression will be used to compare diagnostic performance between groups, with physician seniority included as a fixed effect and physician and case included as random effects. The study will use deidentified clinical cases and will not involve direct patient participation or influence clinical care.
- Conditions
- Chronic Thromboembolic Pulmonary Hypertension (CTEPH), Acute Pulmonary Embolism (PE), Pulmonary Artery Sarcoma
- Being tested
- Locked CTEPH-LLM Diagnostic Decision Support
- Keywords
- Chronic Thromboembolic Pulmonary Hypertension, Pulmonary Embolism, Pulmonary Artery Sarcoma, Differential Diagnosis, Early Identification, Large Language Model, Artificial Intelligence, Multimodal Model
- Medical subject headings
- Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Locked CTEPH-LLM Diagnostic Decision SupportOther
A locked LLM-based decision support system will process the same staged clinical information reviewed by participating clinicians. For each case and stage, the system will display a pre-generated Top-1 diagnosis among CTEPH, acute PE, and PAS; key evidence supporting and opposing that diagnosis; and a referral recommendation. Before randomization, the model name and version, call date, system and user prompts, input fields, context organization, sampling parameters, output format, risk thresholds, and all case-stage outputs will be locked. Outputs will not be selected, repeated, or modified on the basis of participant responses during the study.
| Study group | Role | What they receive |
|---|---|---|
| LLM-Assisted Case Interpretation | Experimental | Clinicians will review the same 30 de-identified cases using the same four-stage sequence and response requirements as the control group. At each stage, they will additionally receive the corresponding locked LLM output, including a Top-1 diagnosis, key supporting and opposing evidence, and referral advice. Clinicians may accept or reject the AI advice and remain responsible for their submitted answers. Receives: Other: Locked CTEPH-LLM Diagnostic Decision Support |
| Standard Case Interpretation | No intervention | Clinicians will review the 30 de-identified cases using the standardized four-stage sequence and will record their Top-1 diagnosis, key diagnostic rationale, referral recommendation, and response time at each stage. They will not have access to the study LLM interface or any other generative AI tool. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage 4 CTEPH Identification Sensitivity
The proportion of evaluable physician-case judgments for the 10 reference-standard CTEPH cases in which the physician's final Top-1 diagnosis after Stage 4 is CTEPH. The numerator is the number of correct CTEPH identifications and the denominator is the number of evaluable Stage 4 judgments for CTEPH cases. The between-group comparison will account for clustering by physician and case.
Measured: At completion of Stage 4 for each case, within 14 days after the clinician's first formal case-reading session
Stage 4 Three-Class Top-1 Diagnostic Accuracy
The proportion of evaluable Stage 4 physician-case judgments in which the clinician's Top-1 diagnosis matches the reference diagnosis among CTEPH, acute PE, and PAS.
Measured: During the two formal case-reading sessions, completed within 14 days after the first session
Secondary outcomes (5)
Stage 4 Class-Specific Diagnostic Performance
For CTEPH, acute PE, and PAS separately, sensitivity, specificity, positive predictive value, and negative predictive value will be calculated from evaluable Stage 4 Top-1 diagnoses against the prespecified reference standard.
Measured: During the two formal case-reading sessions, completed within 14 days after the first session
Diagnostic Response Time
Total response time across all cases and response time at each information stage will be recorded automatically by the study platform. Time will be summarized in seconds or minutes, using means with standard deviations or medians with interquartile ranges as appropriate.
Measured: During the two formal case-reading sessions, completed within 14 days after the first session
Stage-Wise Diagnostic Change
Changes in the clinician's Top-1 diagnosis and recorded diagnostic probabilities from Stage 1 through Stage 4 will be summarized, including the proportion of judgments that change between consecutive stages and between Stage 1 and Stage 4.
Measured: During the two formal case-reading sessions, completed within 14 days after the first session
AI-Assisted Correction Rate When the AI Recommendation Is Correct
Among LLM-assisted judgments in which the clinician's diagnosis before considering the stage-specific AI output is incorrect and the AI Top-1 diagnosis is correct, the proportion in which the clinician submits the correct diagnosis after receiving the AI output.
Measured: During the two formal case-reading sessions, completed within 14 days after the first session
AI-Related Over-Reliance Rate When the AI Recommendation Is Incorrect
Among LLM-assisted judgments in which the clinician's diagnosis before considering the stage-specific AI output is correct and the AI Top-1 diagnosis is incorrect, the proportion in which the clinician changes to the incorrect AI diagnosis after receiving the AI output.
Measured: During the two formal case-reading sessions, completed within 14 days after the first session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2026
- Study start1 Oct 2026 (estimated)
- Primary completion31 May 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Thromboembolic Pulmonary Hypertension (CTEPH)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Clinicians will be stratified by professional seniority and randomized in a 1:1 ratio to LLM-assisted case interpretation or standard case interpretation. Both groups will review the same 30 de-identified cases using the same four-stage information sequence, response fields, timing rules, and permitted non-generative medical resources. Access to the locked LLM output is the only planned difference between groups.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- China-Japan Friendship Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhenguo Zhai,MD,PhD, China-Japan Friendship Hospital
- Investigators
- Zhenguo Zhai, Principal investigator, China-Japan Friendship Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07902011
- Sponsor's protocol ID
- CLEAR Study
- Status last verified
- Jul 2026
- First submitted
- 22 Oct 2026
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Large Language Model-Assisted Differential Diagnosis of Pulmonary Artery Filling Defects: A Stratified Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07902011
- Acronym / sponsor ID
- CLEAR Study
- Conditions
- Chronic Thromboembolic Pulmonary Hypertension (CTEPH), Acute Pulmonary Embolism (PE), Pulmonary Artery Sarcoma
- Keywords
- Chronic Thromboembolic Pulmonary Hypertension, Pulmonary Embolism, Pulmonary Artery Sarcoma, Differential Diagnosis, Early Identification, Large Language Model, Artificial Intelligence, Multimodal Model
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- China-Japan Friendship HospitalUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 31 May 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 28 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized controlled trial aims to evaluate whether a locked large language model (LLM)-based clinical decision support system improves the differential diagnosis of pulmonary artery filling defects among physicians who do not specialize in pulmonary vascular diseases. Participants will evaluate 30 de-identified clinical cases involving chronic thromboembolic pulmonary hypertension (CTEPH), acute pulmonary embolism (PE), and pulmonary artery sarcoma (PAS), with or without LLM assistance. The primary outcome is sensitivity for identifying CTEPH, while secondary outcomes include overall diagnostic accuracy, time to diagnosis, appropriateness of referral recommendations, and AI-related diagnostic errors.
Detailed description
Pulmonary artery filling defects can result from several conditions, including chronic thromboembolic pulmonary hypertension (CTEPH), acute pulmonary embolism (PE), and pulmonary artery sarcoma (PAS). Distinguishing these conditions can be challenging for physicians who do not specialize in pulmonary vascular diseases. This prospective randomized controlled trial aims to assess whether a clinical decision support system using a locked large language model (LLM) can improve diagnostic performance and reduce diagnostic errors. The study will enroll up to 66 physicians, with a target of 60 participants completing the trial. After providing informed consent and completing a baseline assessment, participants will be stratified by professional seniority and randomly assigned in a 1:1 ratio to either an LLM assisted group or a control group. Randomization will be performed using a computer generated sequence, with allocation concealed until baseline assessments are completed. All participants will independently evaluate the same 30 deidentified clinical cases, including 10 cases each of CTEPH, acute PE, and PAS. The diagnoses will be confirmed by relevant specialists using established diagnostic criteria. These cases will not have been used for model development or optimization. Each participant will complete two sessions of 15 cases, separated by 3 to 7 days, with case order randomized for each participant. Clinical information will be presented in four stages: clinical history and physical examination, laboratory findings, echocardiography, and computed tomography pulmonary angiography (CTPA). Participants will record their diagnosis at each stage before receiving additional information. The control group will make diagnostic decisions based on the available clinical information, while the LLM assisted group will also receive the model's most likely diagnosis, supporting and opposing evidence, and referral recommendations. The model version, prompts, parameters, and case specific outputs will be fixed before randomization and remain unchanged throughout the study. The primary outcome is sensitivity for identifying CTEPH after all four stages. Secondary outcomes include diagnostic accuracy across all three conditions, diagnostic performance at each stage, time to diagnosis, appropriateness of referral recommendations, and errors associated with reliance on incorrect LLM recommendations. Analyses will follow the intention to treat principle. Mixed effects logistic regression will be used to compare diagnostic performance between groups, with physician seniority included as a fixed effect and physician and case included as random effects. The study will use deidentified clinical cases and will not involve direct patient participation or influence clinical care.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Clinicians will be stratified by professional seniority and randomized in a 1:1 ratio to LLM-assisted case interpretation or standard case interpretation. Both groups will review the same 30 de-identified cases using the same four-stage information sequence, response fields, timing rules, and permitted non-generative medical resources. Access to the locked LLM output is the only planned difference between groups.
| Arm | Type | Receives |
|---|---|---|
| LLM-Assisted Case Interpretation | Experimental | Other: Locked CTEPH-LLM Diagnostic Decision SupportClinicians will review the same 30 de-identified cases using the same four-stage sequence and response requirements as the control group. At each stage, they will additionally receive the corresponding locked LLM output, including a Top-1 diagnosis, key supporting and opposing evidence, and referral advice. Clinicians may accept or reject the AI advice and remain responsible for their submitted answers. |
| Standard Case Interpretation | No intervention | –Clinicians will review the 30 de-identified cases using the standardized four-stage sequence and will record their Top-1 diagnosis, key diagnostic rationale, referral recommendation, and response time at each stage. They will not have access to the study LLM interface or any other generative AI tool. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Holds a valid physician qualification, or is enrolled in a standardized residency training program and is permitted to participate in clinical care under supervision.
- Has not previously reviewed the validation cases or their final diagnoses.
- Is willing to participate and provides informed consent.
- Is able to use the standardized study platform and complete two formal case-reading sessions covering all 30 cases.
Key exclusion criteria (4 listed)
- Has a specialist professional background in pulmonary vascular disease, pulmonary hypertension, or thoracic imaging.
- Participated in validation-case selection, reference-standard confirmation, model development, prompt optimization, or review of locked model outputs.
- Is unable to use the standardized platform or to comply with independent case interpretation and the prohibition on external generative AI tools.
- Has another circumstance that, in the investigator's judgment, could materially compromise independent case interpretation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Locked CTEPH-LLM Diagnostic Decision SupportA locked LLM-based decision support system will process the same staged clinical information reviewed by participating clinicians. For each case and stage, the system will display a pre-generated Top-1 diagnosis among CTEPH, acute PE, and PAS; key evidence supporting and opposing that diagnosis; and a referral recommendation. Before randomization, the model name and version, call date, system and user prompts, input fields, context organization, sampling parameters, output format, risk thresholds, and all case-stage outputs will be locked. Outputs will not be selected, repeated, or modified on the basis of participant responses during the study. | Other | LLM-Assisted Case Interpretation |
Primary outcome
Stage 4 CTEPH Identification Sensitivity
Time frame: At completion of Stage 4 for each case, within 14 days after the clinician's first formal case-reading session
The proportion of evaluable physician-case judgments for the 10 reference-standard CTEPH cases in which the physician's final Top-1 diagnosis after Stage 4 is CTEPH. The numerator is the number of correct CTEPH identifications and the denominator is the number of evaluable Stage 4 judgments for CTEPH cases. The between-group comparison will account for clustering by physician and case.
Stage 4 Three-Class Top-1 Diagnostic Accuracy
Time frame: During the two formal case-reading sessions, completed within 14 days after the first session
The proportion of evaluable Stage 4 physician-case judgments in which the clinician's Top-1 diagnosis matches the reference diagnosis among CTEPH, acute PE, and PAS.
5 secondary outcomes
Stage 4 Class-Specific Diagnostic Performance
Time frame: During the two formal case-reading sessions, completed within 14 days after the first session
Diagnostic Response Time
Time frame: During the two formal case-reading sessions, completed within 14 days after the first session
Stage-Wise Diagnostic Change
Time frame: During the two formal case-reading sessions, completed within 14 days after the first session
AI-Assisted Correction Rate When the AI Recommendation Is Correct
Time frame: During the two formal case-reading sessions, completed within 14 days after the first session
AI-Related Over-Reliance Rate When the AI Recommendation Is Incorrect
Time frame: During the two formal case-reading sessions, completed within 14 days after the first session
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zhenguo Zhai principal investigator
China-Japan Friendship Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Locked CTEPH-LLM Diagnostic Decision Support in people with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Acute Pulmonary Embolism (PE), run by China-Japan Friendship Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhenguo Zhai (86-10-84206265, zhaizhenguo2011@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage 4 CTEPH Identification Sensitivity (time frame: At completion of Stage 4 for each case, within 14 days after the clinician's first formal case-reading session). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.