Comparison of three diagnostic strategies for suspicion of pulmonary embolism: planar ventilation/perfusion scan, CT pulmonary angiography and single-photon emission CT ventilation/perfusion scan – a multicentre, non-inferiority randomised controlled trial

BACKGROUND: While single-photon emission computed tomography (SPECT) ventilation/perfusion (V/Q) has been widely adopted for pulmonary embolism (PE) diagnosis, it is not currently endorsed by clinical guidelines due to insufficient evidence. METHODS: We conducted a non-inferiority randomised trial comparing SPECT V/Q-, computed tomography pulmonary angiography (CTPA)- and planar V/Q-based diagnostic strategies using a 2:1:1 allocation. The primary end-point was the 3-month risk of venous thromboembolism (VTE) in untreated patients with a negative workup, comparing SPECT V/Q to the combined CTPA and planar V/Q arms. A non-inferiority margin of 1% absolute difference in 3-month VTE risk was defined. Secondary outcomes included PE diagnosis rates. The trial ended prematurely in October 2024 due to slow recruitment and funding limitations. RESULTS: From July 2017 to October 2024, 603 patients were randomised. PE was diagnosed in 61/303 (20.1%) in the SPECT V/Q arm, 31/150 (20.7%) in the CTPA arm and 24/150 (16.0%) in the planar V/Q arm. The 3-month VTE risk in patients left untreated after a negative workup was 0.5% (1/221) for SPECT V/Q, 0.0% (0/107) for CTPA and 0.8% (1/118) for planar V/Q. The difference in outcome between SPECT V/Q and the combined arms was 0.0% (95% CI -1.2-1.3%). CONCLUSION: After being prematurely discontinued, this randomised trial did not demonstrate the non-inferiority of a SPECT V/Q-based strategy to reference standards for PE diagnosis. However, the results suggest a low 3-month VTE risk in patients managed using a SPECT V/Q-based diagnostic strategy. Among patients with clinically suspected acute PE requiring chest imaging, a SPECT V/Q-based algorithm might be a reliable alternative in clinical practice.