Subsegmental Pulmonary Embolism NosPhase 3STOPAPENCT04727437
STOPping Anticoagulation for Isolated or Incidental Subsegmental Pulmonary Embolism
A Phase 3 study testing No treatment, Warfarin and direct oral anticoagulants in people with Subsegmental Pulmonary Embolism Nos, run by University of Birmingham at 1 site in United Kingdom.
Trial summary
Pulmonary embolisms (PE) occur when blood clots cause a blockage of the blood supply to the lungs. A small PE located in the subsegmental pulmonary vasculature is identified as a subsegmental PE (SSPE). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Subsegmental Pulmonary Embolism Nos
- What is being tested?
- No treatment, Warfarin and direct oral anticoagulants
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,466 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 8 Apr 2021to May 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Age ≥18 years
- SSPE diagnosed by the radiologist at the trial site by CTPA or CT thorax with IV contrast
- No evidence of proximal deep vein thrombosis on doppler ultrasonography or CT / Magnetic Resonance venography
- Heart rate (<110bpm)
- Systolic blood pressure (≥100 mmHg)
- Oxygen saturation (≥90%)
- Written signed informed consent to the trial
Who cannot join
- Indication for hospital admission
- >7 days empirical anticoagulation treatment immediately prior to randomisation
- <28 days since first symptoms of proven or clinically suspected Coronavirus disease (COVID-19)
- Known stage 5 chronic kidney disease
- Patients with active cancer defined as cancer diagnosed within the past 6 months, cancer for which anticancer treatment was being given at the time of enrolment or during 6 months before randomisation, or recurrent locally advanced or metastatic cancer
- Patients with previous unprovoked PE, thrombophilia or requiring long term anticoagulation for another reason
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- Patients with a Deep Vein Thrombosis / thrombus of an unusual site (e.g. upper limbs, associated with a line) that requires anticoagulation
- Patients with active bleeding
- Any condition which, in the opinion of the investigator, makes the participant unsuitable for trial entry due to prognosis/terminal illness with a projected survival of less than 3 months
- Pregnancy confirmed by positive pregnancy test or post-partum period or actively trying to conceive
- Inability to comply with the trial schedule and follow-up
- Participation in a Clinical Trial of Investigative Medicinal Product (CTIMP) study
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Surrey & Sussex Healthcare NHS Trust
Redhill, RH1 5RH
Sarah Davies, 01737 768511 ext. 2804, sarah.davies60@nhs.net
Jenny Bacon
About this study
Pulmonary embolisms (PE) occur when blood clots cause a blockage of the blood supply to the lungs. A small PE located in the subsegmental pulmonary vasculature is identified as a subsegmental PE (SSPE). Anticoagulants are used to treat SSPE and work by preventing new clots from forming whilst the body's own mechanisms break down the clots, however they can also increase the risk of major and potentially life threatening bleeding. More recent observational data of routine care for SSPE showed very high complication rates of anticoagulation but in patients where treatment was withheld, this proved to be a safe strategy in terms of recurrent venous thromboembolism (VTE).
Computed tomography pulmonary angiography (CTPA) scans are now able to detect SSPE, however there are concerns that there is an over-diagnosis due to the incorrect interpretation of small artefacts. 1466 patients from approximately 50 sites will be recruited, these sites will consist of hospitals across the United Kingdom (UK). Patients 18 and over with isolated SSPE, confirmed by either CTPA or CT thorax with IV contrast, will be eligible for the trial. Patients will be randomised to either receive standard anticoagulation for at least 3 months (control) or no anticoagulation for at least 3 months (intervention). The participant will receive telephone follow up calls at 4, 12 and 24 weeks following the end of their treatment, and additional data will also be taken from their medical records at these time points. The participant isn't required to be contacted for the 52 week follow up as the data will be extracted from the National Health Service (NHS) Digital collection of Hospital Episode Statistics (HES). In total participation in the study will last 12 months. In addition the cost-effectiveness of no treatment versus treatment with full anticoagulation will be looked at and also improving on radiological diagnosis of SSPE.
- Conditions
- Subsegmental Pulmonary Embolism Nos
- Being tested
- No treatment, Warfarin, direct oral anticoagulants, Low molecular weight heparin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No treatmentOther
Withholding anticoagulation for at least 3 months.
WarfarinDrug
anticoagulation drug given for at least 3 months.
direct oral anticoagulantsDrug
anticoagulation drug given for at least 3 months.
Low molecular weight heparinDrug
anticoagulation drug, subcutaneous injection given for at least 3 months.
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | Full dose anticoagulation treatment as standard care for at least 3 months. Receives: Drug: Warfarin; Drug: direct oral anticoagulants; Drug: Low molecular weight heparin |
| Intervention | Experimental | Withholding anticoagulation for Isolated Sub-Segmental Pulmonary Embolism (ISSPE) for at least 3 months. Receives: Other: No treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
A composite score of the number of recurrent venous thromboembolism and/or clinically relevant bleeding
To determine if withholding anticoagulation is non-inferior to standard anticoagulation therapy in the treatment of isolated or incidental subsegmental pulmonary embolism for preventing recurrent venous thromboembolism, and/or death related and non death related venous thromboembolism, or superior for clinically relevant bleeding over 3 months, compared with at least 3 months of full anticoagulation. This will be measured using a scoring system which is currently being developed by the statistical team, and will be detailed in the statistical analysis plan when finalised.
Measured: 3 months
Secondary outcomes (5)
The change in frequency and severity of harmful events
Determine whether withholding anticoagulation for isolated subsegmental pulmonary embolism reduces harmful events (recurrent venous thromboembolism, clinically relevant bleeding) compared with at least 3 months of full anticoagulation at 6 and 12 months. This will be assessed through Hospital Episode Statistic records.
Measured: 6 and 12 months
Number of new diagnosis of pulmonary hypertension of right ventricular dysfunction identified from Hospital Episode Statistics.
Determine the impact of withholding anticoagulation for isolated subsegmental pulmonary embolism on diagnoses of pulmonary hypertension at 12 months. Measure new diagnosis of pulmonary hypertension or right ventricular dysfunction within 12 months of subsegmental pulmonary embolism, defined from Hospital Episode Statistics clinical coding and supported where possible by additional radiological data and echocardiogram undertaken in tertiary pulmonary hypertension centres. The parameters and variables used to analysed data from the Hospital Episode Statistics are being developed and will be outlined in the statistical analysis plan when finalised.
Measured: 12 months
Reclassification rate from thoracic radiologist review
Determine the reclassification rate of subsegmental pulmonary embolism diagnoses made by acute reporting radiologists when reviewed by thoracic radiologists and formulate a set of rules to improve acute reporting radiologists' diagnoses of subsegmental pulmonary embolism.
Measured: 32 months
Measuring the rate of net clinical benefit
A composite of clinically relevant bleeding and recurrent venous thromboembolism at 3 and 6 months, measured at the 3 and 6 month follow up time points using statistical coding as described in the statistical analysis plan.
Measured: 3 and 6 months
Measuring the rate of mortality
Measurement of all-cause mortality and venous thromboembolism related mortality at 3, 6 and 12 months. Measurement of cardiovascular mortality at 3, 6 and 12 months defined as cardiac deaths (e.g. cardiogenic shock, fatal arrhythmia, cardiac rupture) and vascular deaths (e.g. venous thromboembolism related, fatal stroke, ruptured aortic aneurysm, aortic dissection).
Measured: 3, 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2021
- Study start8 Apr 2021
- Primary completionJul 2023 (estimated)
- Study completionMay 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Subsegmental Pulmonary Embolism NosStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,466 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Royal United Hospitals Bath NHS Foundation Trust, Cimar
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04727437
- Sponsor's protocol ID
- Worktribe 799297
- Other IDs
- 280586, ISRCTN15645679
- Acronym
- STOPAPE
- Status last verified
- Sep 2021
- First submitted
- 7 Jan 2021
- Last updated
- 29 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- STOPping Anticoagulation for Isolated or Incidental Subsegmental Pulmonary Embolism
- ClinicalTrials.gov ID
- NCT04727437
- Acronym / sponsor ID
- STOPAPE / Worktribe 799297
- Conditions
- Subsegmental Pulmonary Embolism Nos
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,466 participants (estimated)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- Royal United Hospitals Bath NHS Foundation Trust, Cimar
- Study start
- 8 Apr 2021 (actual)
- Primary completion
- Jul 2023 (estimated)
- Study completion
- May 2024 (estimated)
- First posted
- 27 Jan 2021 (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.
Pulmonary embolisms (PE) occur when blood clots cause a blockage of the blood supply to the lungs. A small PE located in the subsegmental pulmonary vasculature is identified as a subsegmental PE (SSPE). Anticoagulants are used to treat SSPE and work by preventing new clots from forming whilst the body's own mechanisms break down the clots, however they can also increase the risk of major and potentially life threatening bleeding. More recent observational data of routine care for SSPE showed very high complication rates of anticoagulation but in patients where treatment was withheld, this proved to be a safe strategy in terms of recurrent venous thromboembolism (VTE).
Computed tomography pulmonary angiography (CTPA) scans are now able to detect SSPE, however there are concerns that there is an over-diagnosis due to the incorrect interpretation of small artefacts. 1466 patients from approximately 50 sites will be recruited, these sites will consist of hospitals across the United Kingdom (UK). Patients 18 and over with isolated SSPE, confirmed by either CTPA or CT thorax with IV contrast, will be eligible for the trial. Patients will be randomised to either receive standard anticoagulation for at least 3 months (control) or no anticoagulation for at least 3 months (intervention). The participant will receive telephone follow up calls at 4, 12 and 24 weeks following the end of their treatment, and additional data will also be taken from their medical records at these time points. The participant isn't required to be contacted for the 52 week follow up as the data will be extracted from the National Health Service (NHS) Digital collection of Hospital Episode Statistics (HES). In total participation in the study will last 12 months. In addition the cost-effectiveness of no treatment versus treatment with full anticoagulation will be looked at and also improving on radiological diagnosis of SSPE.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Active comparator | Drug: Warfarin, Drug: direct oral anticoagulants, Drug: Low molecular weight heparinFull dose anticoagulation treatment as standard care for at least 3 months. |
| Intervention | Experimental | Other: No treatmentWithholding anticoagulation for Isolated Sub-Segmental Pulmonary Embolism (ISSPE) for at least 3 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥18 years
- SSPE diagnosed by the radiologist at the trial site by CTPA or CT thorax with IV contrast
- No evidence of proximal deep vein thrombosis on doppler ultrasonography or CT / Magnetic Resonance venography
- Heart rate (<110bpm)
- Systolic blood pressure (≥100 mmHg)
Key exclusion criteria (12 listed)
- Indication for hospital admission
- >7 days empirical anticoagulation treatment immediately prior to randomisation
- <28 days since first symptoms of proven or clinically suspected Coronavirus disease (COVID-19)
- Known stage 5 chronic kidney disease
- Patients with active cancer defined as cancer diagnosed within the past 6 months, cancer for which anticancer treatment was being given at the time of enrolment or during 6 months before randomisation, or recurrent locally advanced or metastatic cancer
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 |
|---|---|---|
| No treatmentWithholding anticoagulation for at least 3 months. | Other | Intervention |
| Warfarinanticoagulation drug given for at least 3 months. | Drug | Control |
| direct oral anticoagulantsanticoagulation drug given for at least 3 months. | Drug | Control |
| Low molecular weight heparinanticoagulation drug, subcutaneous injection given for at least 3 months. | Drug | Control |
Primary outcome
A composite score of the number of recurrent venous thromboembolism and/or clinically relevant bleeding
Time frame: 3 months
To determine if withholding anticoagulation is non-inferior to standard anticoagulation therapy in the treatment of isolated or incidental subsegmental pulmonary embolism for preventing recurrent venous thromboembolism, and/or death related and non death related venous thromboembolism, or superior for clinically relevant bleeding over 3 months, compared with at least 3 months of full anticoagulation. This will be measured using a scoring system which is currently being developed by the statistical team, and will be detailed in the statistical analysis plan when finalised.
5 secondary outcomes
The change in frequency and severity of harmful events
Time frame: 6 and 12 months
Number of new diagnosis of pulmonary hypertension of right ventricular dysfunction identified from Hospital Episode Statistics.
Time frame: 12 months
Reclassification rate from thoracic radiologist review
Time frame: 32 months
Measuring the rate of net clinical benefit
Time frame: 3 and 6 months
Measuring the rate of mortality
Time frame: 3, 6 and 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2021.
- Individual participant dataSharing planned: Yes
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Diagnostic Value of Photon-Counting CT in Subsegmental Pulmonary Embolism
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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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing No treatment, Warfarin and direct oral anticoagulants in people with Subsegmental Pulmonary Embolism Nos, run by University of Birmingham at 1 site in United Kingdom.
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 7 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 29 Sep 2021. 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 United Kingdom. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pooja Gaddu (01214159120, p.gaddu@bham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A composite score of the number of recurrent venous thromboembolism and/or clinically relevant bleeding (time frame: 3 months). 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 Sep 2021.