Ignite Creation Date:
2026-03-26 @ 3:19 PM
Ignite Modification Date:
2026-03-31 @ 1:25 PM
Study NCT ID:
NCT07491094
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-24
First Post:
2026-03-11
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Repeated Examinations for Typing Pulmonary Embolism
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011655', 'term': 'Pulmonary Embolism'}, {'id': 'D004194', 'term': 'Disease'}, {'id': 'D000075902', 'term': 'Clinical Deterioration'}, {'id': 'D003643', 'term': 'Death'}], 'ancestors': [{'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D004617', 'term': 'Embolism'}, {'id': 'D016769', 'term': 'Embolism and Thrombosis'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D018450', 'term': 'Disease Progression'}, {'id': 'D020969', 'term': 'Disease Attributes'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood samples for analysis of Troponin I (TnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and lactate will be obtained three times during the inclusion day (day 0) and once day 1 and 2. Blood samples for biobanking will be obtained day 0, 1 and 2 (metabolomics, proteomics, circulating miRNA and mRNA).'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 400}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-04-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-03', 'completionDateStruct': {'date': '2032-01-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-03-19', 'studyFirstSubmitDate': '2026-03-11', 'studyFirstSubmitQcDate': '2026-03-19', 'lastUpdatePostDateStruct': {'date': '2026-03-24', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-24', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2030-01-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Clinical deterioration', 'timeFrame': '7 days', 'description': 'The composite of: All-cause death, cardiac arrest, hemodynamic decompensation (systolic blood pressure \\<90 mmHg, need of vasopressor, clinical signs of hypoperfusion or fall of systolic blood pressure \\>40 mmHg in 15 minutes), respiratory failure (need of respiratory support such as high-flow nasal oxygen, non-invasive ventilation or intubation), escalation to rescue reperfusion therapy (thrombolysis, thrombectomy/FlowTriever, surgery), National Early Warning Score 2 (NEWS2) -score ≥7 or transfer to intensive care unit ("IVA" as defined at Sahlgrenska) due to PE. Each individual outcome will also be analysed independently.'}, {'measure': 'Major bleeding', 'timeFrame': '7 days', 'description': 'According to ISTH (International Society on Thrombosis and Haemostasis) as fatal bleeding, and/or symptomatic bleeding in a critical area or organ (such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial), or intramuscular with compartment syndrome, and/or bleeding causing a fall in hemoglobin levels of 20 g/L or greater, or leading to a transfusion of 2 units or more of whole blood or red cells.'}], 'secondaryOutcomes': [{'measure': 'The composite of death, VTE recurrence or major bleeding', 'timeFrame': '30 days', 'description': 'Death (all-cause), recurrent VTE or major bleeding (according to ISTH)'}, {'measure': 'The composite of death, VTE recurrence or major bleeding', 'timeFrame': '90 days', 'description': 'Death (all-cause), recurrent VTE or major bleeding (according to ISTH)'}, {'measure': 'Chronic ThromboEmbolic Pulmonary Hypertension (CTEPH)', 'timeFrame': '180 days', 'description': 'Patient medical chart CTEPH diagnosis at long-term follow up'}, {'measure': 'Patient reported outcome measures (PROMs)', 'timeFrame': '90 days', 'description': 'According to Pulmonary Embolism Quality of Life score (PEmb-QoL)'}, {'measure': 'Patient reported outcome measures (PROMs)', 'timeFrame': '90 days', 'description': 'According to Post-Venous Thromboembolism Functional Status scale (PVFS)'}, {'measure': 'Patient reported outcome measures (PROMs)', 'timeFrame': '90 days', 'description': 'EuroQol 5-Dimension (EQ5D) questionnaire'}, {'measure': 'Admission rate for low risk PE', 'timeFrame': '365 days', 'description': 'Admission rate (patients admitted/diagnosed) for low risk symtomatic or low risk incidental PE'}, {'measure': 'Outcome for low risk PE', 'timeFrame': '365 days', 'description': 'Clinical outcome (composite of death, recurrent VTE or major bleeding) for low risk symtomatic PE or low risk incidental PE'}, {'measure': 'Clinically relevant non-major bleeding (CRNMB)', 'timeFrame': '365 days', 'description': 'Clinically relevant non-major bleeding (CRNMB, Kaatz et al 2015) defined as any overt sign of hemorrhage that does not meet the criteria for major bleeding, but requires a medical intervention, such as a face-to-face evaluation or hospitalization.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Echocardiography', 'Point Of Care UltraSound (POCUS)', 'Electrocardiography (ECG)', 'Biomarkers/Blood', 'Troponin I', 'NT-pro-BNP', 'Lactate', 'Prediction model', 'Clinical deterioration', 'Death'], 'conditions': ['Pulmonary Embolism (Diagnosis)', 'Pulmonary Embolism Acute', 'Pulmonary Embolism With Acute Cor Pulmonale', 'Pulmonary Embolism With Right Ventricle Enlargement', 'Pulmonary Embolism (PE)']}, 'descriptionModule': {'briefSummary': 'PURPOSE\n\nThe two related purposes of the RE-TyPE study are:\n\n1. To improve understanding of the early clinical course of intermediate-high risk pulmonary embolism and its association with outcome and\n2. To establish a platform for longitudinal follow-up for all pulmonary embolism at Sahlgrenska University Hospital\n\nHYPOTHESES\n\n1. The dynamic pattern of change, evaluated thorough repeated measures of biomarkers, electrocardiography and echocardiography during the first 48 hours after pulmonary embolism, better predicts outcome than static measurements currently used to predict outcome\n2. Establishment of a platform for longitudinal follow-up will improve quality of care and outcome for patients with pulmonary embolism at Sahlgrenska University Hospital', 'detailedDescription': 'BACKGROUND\n\nPulmonary embolism (PE) is the third most common acute cardiovascular condition and remains associated with substantial morbidity and mortality. Although advances in therapy have reduced overall mortality, optimal treatment within the intermediate-high risk group remains uncertain. In parallel, knowledge of long-term outcomes after PE in Sweden is incomplete, largely due to the absence of a dedicated national PE registry.\n\nRisk stratification of PE has evolved into the current four-tier European Society of Cardiology (ESC) classification, supported by clinical risk scores such as the Pulmonary Embolism Severity Index (PESI). The intermediate-high risk group is especially challenging due to marked heterogeneity in clinical course, ranging from rapid recovery to sudden deterioration. Existing risk scores were mainly developed to identify low risk patients and provide limited guidance on predicting deterioration, largely due to low positive predictive value.\n\nCurrent risk stratification relies on static, single-timepoint variables, despite PE being a dynamic disease. Prospective studies evaluating the early temporal course of PE are scarce and typically focus on isolated parameters, with no studies integrating repeated clinical, imaging, and biomarker assessments.\n\nThe RE-TyPE study aims to address these gaps by characterizing the early clinical course of intermediate-high risk PE and linking this to short- and medium-term outcomes. The study will also provide a platform for long-term follow-up, evaluation of treatment strategies, and a research infrastructure dedicated to all PE at Sahlgrenska University Hospital.\n\nAIM, OBJECTIVES AND METHODS\n\nThe overarching research aim is to characterize the early clinical course of intermediate-high risk PE to identify phenotypes associated with poor outcome (Cohort A), and to investigate intermediate- and long-term outcome and outpatient care for all PE cases at Sahlgrenska University Hospital (Cohort B).\n\nPRIMARY OBJECTIVES\n\nCohort A - prospective phenotyping (admitted intermediate-high risk PE):\n\nTo collect in-dept data regarding the early clinical course of PE, including temporal changes in vital signs, ECG, echocardiography and biomarkers from baseline (day 0, PE-event) until day 2, and to analyse its association with in-hospital clinical outcome day 0-7.\n\nCohort B - follow-up (all PE):\n\nTo collect in-dept baseline data, including vital signs, ECG, echocardiography and biomarkers, and to analyse its association with intermediate and long-term outcome (\\>12 months)\n\nSCEONDARY OBJECTIVES\n\nCohort A - prospective phenotyping:\n\n1. To collect in-dept data regarding the early clinical course of PE, including temporal changes in vital signs, ECG, echocardiography and biomarkers from baseline (day 0, PE-event) until day 2, and to analyse its association with clinical outcome at day 30\n2. To examine the timing of thrombolysis and/or thrombectomy in relation to in-hospital (day 0-7), short-term (day 30) and medium-term (\\~90 days) outcome\n3. To investigate the association between simple walking test with pulse oximetry, sit-to-stand test (drop of saturation, heartrate) or 6-minute walking test (walking distance, drop of oxygen saturation and heart rate) and clinical outcomes within 7, 30 and \\~90 days respectively\n4. To investigate the value of in-hospital simple walking test with pulse oximetry in predicting clinical outcomes in-hospital (day 0-7), short-term (day 30) and medium-term (\\~90 days) outcome\n5. To investigate the correlation between radiological signs of right ventricular strain (increased right ventricle/left ventricle, RV/LV, -ratio and echocardiographic signs of right ventricular strain\n\nCohort B - registry (all PE)\n\nB. Cohort B - follow-up (all PE)\n\n1. Evaluate prognostic implications of clinical phenotypes (based on clinical course for cohort A and based on baseline variables for cohort B) by assessing associations with long-term (1-year) patient-reported outcome measures (PROMs) according to the Pulmonary Embolism Quality of Life Questionnaire (PEmb-QoL), Post Vte Functional Scale (PVFS) or EuroQol 5-Dimension (EQ5D) questionnaire.\n2. Evaluate prognostic implications of clinical phenotypes (based on clinical course day 0-2 for cohort A and based on baseline variables day 0 for cohort B) by assessing associations with long-term (1-year) outcome including CTEPH as well as mortality, recurrent VTE and bleeding.\n3. To assess admission rate and outcome for low risk symtomatic and low risk incidental PE\n\nSTUDY DESIGN\n\nThe RE-TyPE study combines two observational study approaches:\n\nA) A prospective observational cohort study of hospitalized patients with intermediate-high risk PE\n\nand\n\nB) A follow-up cohort including all patients diagnosed with PE at Sahlgrenska University Hospital.\n\nProspective observational study (Cohort A)\n\nHospitalized patients with intermediate-high risk PE at any of the three sites of Sahlgrenska University Hospital (Sahlgrenska, Östra or Mölndal) are eligible for inclusion within 48 hours of PE event (patients included 24-48 hours post PE will be considered late inclusions and will enter the study at day 1). This constitutes patients presenting with primary PE as well as patients who are admitted for other causes and suffer from PE while admitted. Inclusion will be performed Mondays to Fridays.\n\nAfter verbal and written informed consent, the patient will be included in RE-TyPE cohort A and undergo serial repeated examinations day 0 (admission), day 1 (24 ± 6h) and day 2 (48 ± 12h), including vital parameters; pharmacologic treatment including oxygen therapy, thrombolysis and thrombectomy; respiratory and circulatory support; echocardiography, ECG, laboratory blood work-up, blood samples for biobanking, complications and outcome.\n\nThe majority of examinations will be performed at the hospital ward where the patient is admitted. Full echocardiographic evaluation at baseline (day 0) will be performed at the department of Clinical Physiology whereas follow-up echocardiographic examinations day 1 and 2 will be performed bedside (Point Of Care UltraSound, POCUS) at the ward where the patient is admitted. Follow-up will be scheduled to 30 (± 48h) and approximately day 90 (routine clinical follow-up).\n\nPE follow-up cohort (Cohort B)\n\nCohort B constitutes all PE patients diagnosed at Sahlgrenska University Hospital. Therefore, all patients in Cohort A are also included in Cohort B. Patients only included in Cohort B (i.e. not existing in Cohort A) are patients with low, intermediate-low or high risk PE, or patients with intermediate-high risk PE who were not identified for inclusion (i.e. missed cases eligible for Cohort A).\n\nPE patients discharged from the emergency department (ED) or admitted low-risk PE may be included in Cohort B after informed consent during ED visit or hospitalization. However, they will mainly be included at their outpatient follow-up visit (provided they are alive and registered as living within the area covered by Sahlgrenska University Hospital). Only patients in Cohort A will be subjected to the prospective serial evaluations explained above. The PE patients outside of Cohort A will be "follow-up only" patients. For these patients, only baseline day 0, day 90 and long-term variables will be collected.\n\nCancer associated PE\n\nPatients who suffer from PE during active oncologic treatment are managed by the Department of Oncology at Sahlgrenska University Hospital. Aside from the oncologic treatment, the oncology department also handles the treatment and follow-up of the PE (sometimes in collaboration with consults at the internal medicine department). To bridge this gap, we will establish a collaboration with the oncology department regarding RE-TyPE, which will involve a specific contact person at the Department of Oncology regarding this study. Patients with cancer associated PE are eligible for inclusion in Cohort A or B.\n\nAnalytical and statistical considerations\n\nThe clinical course (PE phenotype) during day 0-2 will be characterized by recovery or persistence of right ventricular dysfunction, ECG changes, and biomarker levels. Right ventricular function will be assessed by TAPSE and RV/LV ratio; ECG findings include septal T-wave inversions, S1Q3T3 pattern, and right axis deviation; biomarkers include lactate, NT-proBNP and troponin I.\n\nBecause measurements are repeated over time, mixed-effects models will be used to estimate average levels and trajectories. Linear mixed models will be applied for continuous variables and generalized mixed models for binary variables.\n\nAssociations between phenotype (early clinical course day 0-2) and subsequent outcome (day 2-7) will be analysed using joint models combining mixed-effects models with Cox regression. Multivariable models will adjust for baseline confounders including age, sex, PE risk class, cancer, thrombus burden and reperfusion therapy.\n\nThe sample size will be based on the association between clinical course and the primary clinical outcome (clinical deterioration). In Cohort A, the expected 7-day deterioration is approximately 10%. The sample size calculation is based on a binary predictor (e.g. "severe clinical phenotype" yes or no), and an expected 6% vs 14% clinical deterioration proportion in the non-severe vs severe group (corresponding to 10% total outcome). Using a two-sided α = 0.05, 80% power, and an expected hazard ratio (HR) of approximately 2.5 the required sample size would be slightly over 350 patients. Adding the possibility of 10-15% of the events occurring before day two, 400 patients would be an optimal sample size (https://riskcalc.org/samplesize/).\n\nCENTRAL DEFINITIONS\n\nMain definitions\n\n* Low risk PE: Hemodynamic stable, normal right ventricular function, cardiac biomarkers normal/low (clinical risk scores low)\n* Intermediate-low risk PE: Hemodynamic stable, either right ventricular dysfunction or positive cardiac biomarkers\n* Intermediate-high risk PE: Hemodynamic stable, right ventricular dysfunction and positive cardiac biomarkers\n* High risk PE: Hemodynamic instability, right ventricular dysfunction and positive cardiac biomarkers\n* Hemodynamic instability: Systolic BP \\< 90 mmHg for \\>15 minutes, or need for vasopressors, or Signs of shock\n* ISTH definition for major bleeding: Clinically overt bleeding that is fatal; or occurs in a critical area or organ; or is associated with a fall in haemoglobin of \\>20 g/L; or leading to transfusion of ≥ 2 units of blood.\n\nPRELIMINARY RESULTS\n\nWithin in the intermediate-high risk group of PE, current ESC risk stratification method, combining right ventricular dysfunction with biomarkers suggesting myocardial injury, has insufficient positive predictive value to detect who will deteriorate or not. No markers in isolation or in combination have proven sufficient to predict which patients will deteriorate. Risk prediction tools such PESI has also displayed low positive predictive value for detecting patients who will need more advanced treatment. This further emphasizes the relevance of the RE-TyPE project.\n\nThe RE-TyPE protocol is finalized and an application for ethical approval has been submitted to the Swedish Ethical Review Authority (registration number 2026-00503-01).\n\nETHICAL CONSIDERATIONS\n\nPatients will be included after verbal and written informed consent. The principal investigators and co-investigators (physicians as well as nurses) involved in the study may include patients. The added examinations outside of clinical routine carry no risk for serious adverse events. The study will be launched after ethical approval and will be conducted in accordance with the declaration of Helsinki. Contact has been established with Gothia Forum regarding this specific project for quality assurance.\n\nSCIENTIFIC IMPORTANCE\n\nRE-TyPE is the first study to perform serial investigations using multiple modalities to phenotype PE. This approach with serial investigations of intermediate-high risk PE enables a unique possibility of linking high resolution clinical phenotyping with early, intermediate and long-term outcome. There are numerous studies on single time-point predictors. In contrast to these static measurements, RE-TyPE captures dynamic disease patterns, enabling identification of distinct clinical phenotypes defined by their trajectories rather than static measurements. Also, the follow-up part of RE-TyPE (Cohort B) provide knowledge regarding intermediate- and long-term outcome and enables evaluation of the regional outpatient clinical care of PE patients. If successful, the RE-TyPE-study could significantly improve the quality and safety of care for PE patients.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Adult patients diagnosed with pulmonary embolism during routine clinical care at Sahlgrenska University Hospital in Gothenburg. Patients are identified through hospital services responsible for the diagnosis and management of pulmonary embolism within the regional healthcare system of Region Västra Götaland (Sweden).', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Adult patients (≥ 18 years old) who is diagnosed with, or followed as out-patients for, PE at Sahlgrenska University Hospital\n2. Written informed consent\n\nExclusion Criteria from Cohort A:\n\n1. Low risk, intermediate-low risk or high risk PE\\*\n2. \\>48 hours since arrival to hospital\n3. Expected inability to comply with the protocol (e.g. dementia)\n\nThere are no exclusion criteria from Cohort B. Patients in Cohort B who are not part of Cohort A may be included at diagnosis (day 0) or at follow-up (\\~day 90).\n\n\\*If biomarkers (and/or echocardiography) are not available in hemodynamically stable patients, RV/LV-ratio \\>1 will be considered as preliminary intermediate-high risk. If biomarkers later fall out negative, the patient will be considered as intermediate-low risk and will be moved to Cohort B'}, 'identificationModule': {'nctId': 'NCT07491094', 'acronym': 'RE-TyPE', 'briefTitle': 'Repeated Examinations for Typing Pulmonary Embolism', 'organization': {'class': 'OTHER', 'fullName': 'Sahlgrenska University Hospital'}, 'officialTitle': 'Repeated Examinations for Typing Pulmonary Embolism (RE-TyPE)', 'orgStudyIdInfo': {'id': '2026-00503-01 (registr. nr.)'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Cohort A', 'description': 'Intermediate-high risk pulmonary embolism - prospective phenotyping thorugh serial investigations day 0, 1, 2 30 and 90.'}, {'label': 'Cohort B', 'description': 'All risk classes of pulmonary embolism - retrospective and prospective phenotyping at day 0, 90 (inclusion) and \\>12 months (Cohorts overlap since all patients in Cohort A are also part of Cohort B)'}]}, 'contactsLocationsModule': {'locations': [{'city': 'Gothenburg', 'state': 'Region Västra Götaland', 'country': 'Sweden', 'facility': 'Sahlgrenska University Hospital/Mölndal', 'geoPoint': {'lat': 57.70716, 'lon': 11.96679}}, {'city': 'Gothenburg', 'state': 'Region Västra Götaland', 'country': 'Sweden', 'contacts': [{'name': 'Rickard Zeijlon, MD, PhD', 'role': 'CONTACT', 'email': 'rickard.zeijlon@vgregion.se', 'phone': '+46705821889'}], 'facility': 'Sahlgrenska University Hospital/Sahlgrenska', 'geoPoint': {'lat': 57.70716, 'lon': 11.96679}}, {'city': 'Gothenburg', 'state': 'Region Västra Götaland', 'country': 'Sweden', 'facility': 'Sahlgrenska University Hospital/Östra', 'geoPoint': {'lat': 57.70716, 'lon': 11.96679}}], 'centralContacts': [{'name': 'Rickard Zeijlon, MD, PhD', 'role': 'CONTACT', 'email': 'rickard.zeijlon@vgregion.se', 'phone': '+46313428884'}, {'name': 'Mazdak Tavoly, MD, PhD', 'role': 'CONTACT', 'phone': '+46313421000'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Sahlgrenska University Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Gothia Forum - Center for Clinical Trial', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Consultant in Internal Medicine, Clinical Postdoctoral Researcher and Principal Investigator', 'investigatorFullName': 'Rickard Zeijlon', 'investigatorAffiliation': 'Sahlgrenska University Hospital'}}}}