STOPping Anticoagulation for Isolated or Incidental Subsegmental Pulmonary Embolism

NCT04727437 | Unknown Phase 3 DMC

• 3 other identifiers: Worktribe 799297280586ISRCTN15645679
• Study Type: interventional
• Target: 1,466
• Locations: 1 country
• Sites: 1

Brief 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). 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

Outcome Measures

Primary Outcomes (1)

• 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.

  3 months

Secondary Outcomes (5)

• The change in frequency and severity of harmful events

  6 and 12 months

• Number of new diagnosis of pulmonary hypertension of right ventricular dysfunction identified from Hospital Episode Statistics.

  12 months

• Reclassification rate from thoracic radiologist review

  32 months

• Measuring the rate of net clinical benefit

  3 and 6 months

• Measuring the rate of mortality

  3, 6 and 12 months

Other Outcomes (3)

• Healthcare resource use and cost

  12 months

• Behavioural analysis of the participants

  32 months

• Behavioural analysis of the healthcare professionals

  32 months

Study Arms (2)

Control

ACTIVE COMPARATOR

Full dose anticoagulation treatment as standard care for at least 3 months.

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.

Other: No treatment

Interventions

No treatment OTHER

Withholding anticoagulation for at least 3 months.

Intervention

Warfarin DRUG

anticoagulation drug given for at least 3 months.

Control

direct oral anticoagulants DRUG

anticoagulation drug given for at least 3 months.

Control

Low molecular weight heparin DRUG

anticoagulation drug, subcutaneous injection given for at least 3 months.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Birmingham: lead
• Royal United Hospitals Bath NHS Foundation Trust: collaborator
• Cimar: collaborator

Study Sites (1)

Surrey & Sussex Healthcare NHS Trust

Redhill, RH1 5RH, United Kingdom

RECRUITING

MeSH Terms

Interventions

Warfarin; N(4)-oleylcytosine arabinoside; Heparin, Low-Molecular-Weight

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Central Study Contacts

Pooja Gaddu

CONTACT

01214159120; p.gaddu@bham.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 27, 2021
• Study Start: April 8, 2021
• Primary Completion: July 1, 2023
• Study Completion: May 1, 2024
• Last Updated: September 29, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)