STOPping Anticoagulation for isolated or incSTOP-APE logoidental subsegmental Pulmonary Embolism

Covid-19: We are now home based during the Covid-19 pandemic but are available and working. Responses may however take longer than normal as staff may be working altered hours but we are cross covering trials as required and urgent matters will be dealt with promptly. Please do not contact our usual office/landline number and instead email the trial contact and copy in the trial mailbox. If a query requires a prompt response please mark as 'Urgent' in the email subject header.



STOP-APE is a multicentre, prospective, randomised controlled, open-label, pragmatic clinical trial designed to test both the non-inferiority and superiority objectives.  A 12-month internal pilot will assess feasibility and acceptability with safety of randomisation based on acute reporting radiologists’ diagnoses assessed as part of a nested computed tomography pulmonary angiogram (CTPA) study.

Aim of the Study

The aim of STOP-APE is to determine if withholding anticoagulation for the treatment of isolated or incidental subsegmental pulmonary embolism (SSPE) is better than treating it with standard anticoagulation therapy.


There will be approximately 50 trial sites from secondary care clinical settings of emergency departments, ambulatory care and acute medical units within NHS hospitals in the UK.

Target Population

1466 consenting adult patients with isolated or incidental SSPE diagnosed on computed tomography pulmonary angiogram (CTPA) or computed tomography (CT) thorax with intravenous (IV) contrast.

Measurement of outcomes

Primary Outcome:

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 (VTE), or death related VTE, or superior for clinically relevant bleeding over 3 months, compared with at least 3 months of full anticoagulation.


Secondary Outcomes:

These objectives are measured 4, 12, 24 and 52 weeks post randomisation. There are multiple secondary objectives for the study, including economic and behavioural objectives.

  • Recurrent VTE or clinically relevant bleeding at 6 months and 12 months (as assessed through HES records).
  • Net clinical benefit - composite of clinically relevant bleeding and recurrent VTE at 3 and 6 months.
  • New diagnosis of pulmonary hypertension or right ventricular dysfunction within 12 months of SSPE, defined from HES clinical coding and supported where possible by additional radiological data and echocardiograms undertaken in tertiary pulmonary hypertension centres. 
  • All-cause mortality at 3, 6 and 12 months.
  • VTE related mortality at 3, 6 and 12 months.
  • 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. VTE-related, fatal stroke, ruptured aortic aneurysm, aortic dissection). 
  • Reclassification rate from thoracic radiologist review.


Economic Objectives:

  • Healthcare resource use: hospitalisations, bed days, unscheduled primary and secondary care visits for recurrent VTE, clinically relevant bleeding or potentially related symptoms. 
  • Healthcare costs. 
  • Health-related quality of life (EQ-5D-5L at baseline, 3 and 6 months).
  • Cost-utility at 6 months (cost per QALY) and cost-effectiveness at 12 months (cost per VTE avoided).


Mechanistic (behavioural) Objectives:

  • Themes from qualitative interviews which inform optimal recruitment strategies including information presentation and attitudes to risk.

 Chief Investigator: Professor Daniel Lasserson

Trial Sponsor: University of Birmingham

 Coordinating Centre: Birmingham Clinical Trials Unit (BCTU) 

Funding: The National Institute for Health Research Health Technology Assessment (NIHR HTA)

Research Ethics Committee: Wales REC 6 (20/WA/0256)

ISRCTN ID: 15645679

NIHR study ID: 46105