Background
Cancer and venous thromboembolism
Treatment of VTE in cancer patients
Study | n | Population | Treatments | Follow-up | Outcomes | Key limitations compared with the CATCH study design |
---|---|---|---|---|---|---|
CLOT [28] | 672 | Acute symptomatic proximal DVT and/or PE | Dalteparin qd (5–7 days) + warfarin* (6 months) | 6 months |
Recurrent VTE (primary)
15.8% (W), 8.0% (D); P = 0.002 | Full-dose dalteparin not maintained for entire 6-month treatment period |
Dalteparin qd (6 months)†
|
Major bleeding
4% (W), 6.0% (D); P = 0.27 | No outcomes for PTS, HRQoL, predictors of recurrence, and healthcare resource utilisation | ||||
Main-LITE‡[27] | 200 | Proximal DVT | UFH + warfarin (6 days) then warfarin (3 months) | 3 months and 12 months |
Recurrent VTE (primary)
3 months: 10.0% (W), 6.0% (T) 12 months: 16.0% (W), 7.0% (T); P = 0.044 | Duration of randomised treatment only 3 months |
Tinzaparin qd (3 months) |
Major bleeding
3 months: 7.0% (W), 7.0% (T) | Modest sample size with limited statistical power | ||||
CANTHANOX [29] | 146 | DVT and/or PE | Enoxaparin qd (initial) + warfarin (3 months) | 3 months |
Treatment failure
§
(primary)
21.1% (W), 10.5% (E); P = 0.09 | Composite primary endpoint (recurrent VTE and major bleeding) |
Enoxaparin qd (3 months) |
Major bleeding
16.0% (W), 7.0% (E); P = 0.09 | Duration of randomised treatment only 3 months Small study with limited statistical power Trial stopped early because of slow recruitment | ||||
ONCENOX [26] | 122 | Acute symptomatic VTE | Enoxaparin LD bid (5 days) + warfarin (6 months) | 6 months |
Recurrent VTE (secondary)
10.0% (W), 6.9% (LD), 6.3% (HD) | Recurrent VTE was only a secondary objective (study did not meet its primary objective, which was to recruit the necessary number of patients within a 12-month time frame) Small study with limited statistical power |
Enoxaparin LD bid (5 days) then LD qd (6 months) | ||||||
Enoxaparin LD bid (5 days) then HD qd (6 months) |
Major bleeding
2.9% (W), 6.5% (LD), 11.1% (HD) |
Main study objectives
Methods
Study design
Study population
VTE before randomisation | Recurrent VTE after randomisation | |
---|---|---|
Symptomatic VTE | • All patients must have diagnostic imaging performed of both legs and the lungs in order to determine baseline presence or absence of DVT or PE. | • Standard objective imaging is required to diagnose recurrent VTE. If there are symptoms from the leg(s) AND lungs, objective imaging is required for both sites. |
• Diagnostic imaging results for DVT: | • Diagnostic imaging results for recurrent DVT: | |
- A non-compressible venous segment of the proximal deep veins in the legs, including iliac, femoral and popliteal veins. | - A non-compressible venous segment of the deep veins (proximal and/or distal) in the legs that had normal compression at baseline. | |
- An intraluminal filling defect on venography, CT scan or MR venography of the proximal deep veins in the leg. | - A new or extension of 5 cm or greater of intraluminal filling defect on venography, CT scan or MR venography of the deep veins in the leg, including inferior vena cava. | |
• Diagnostic imaging results for PE: | - An extension of non-visualisation of the deep veins of the leg in the presence of a sudden cut-off on venography, CT scan or MR venography. | |
- An intraluminal filling defect on CT pulmonary angiography. | • Diagnostic imaging results for recurrent PE: | |
- A perfusion defect of at least 75% of a segment with a local normal ventilation result (mismatch defect) on ventilation-perfusion lung scintigraphy (high-probability scan). | - A new or extension of an existing intraluminal filling defect on CT pulmonary angiography. | |
- A non-high, non-diagnostic ventilation-perfusion lung scan with confirmed DVT. | - A new sudden cut-off of vessels more than 2.5 mm in diameter on CT pulmonary angiography. | |
- A new perfusion defect of at least 75% of a segment with a local normal ventilation result (mismatch defect) on ventilation-perfusion lung scintigraphy (high-probability scan). | ||
- A non-high, non-diagnostic ventilation-perfusion lung scan with confirmed DVT. | ||
• Diagnostic criteria for fatal PE: | ||
- Objective testing as above associated with death. | ||
- Autopsy finding of PE contributing to death. | ||
- Sudden and unexplained death within the 6-month study period which cannot be attributed to a documented cause and for which PE is the most probable cause. | ||
Incidental VTE | • Not valid as an inclusion criterion. | • Incidental PE or DVT are defined as thrombi that were reported during imaging testing performed for reasons other than for suspected PE or DVT. |
• Diagnosis of incidental VTE during the required baseline imaging represents the baseline status. | • The same diagnostic imaging criteria for recurrent DVT or PE apply to confirming the presence of an incidental DVT or PE. | |
• Incidental DVT is only included as an outcome if located in the popliteal or more proximal leg veins. | ||
• Incidental PE is only included as an outcome if located in segmental or more proximal pulmonary arteries. | ||
• In patients with incidental PE involving subsegmental pulmonary arteries only, a compression ultrasound showing a new DVT is necessary to confirm a recurrent thrombotic event. |
Consent
Randomisation and concealment
Study treatments
175 IU/kg body weight subcutaneously once daily | ||||
---|---|---|---|---|
Syringe size | Body weight (kg) rounded up or down to nearest kg | Units | Volume to expel from syringe prior to injection (mL) | Injection volume (mL) |
10,000 IU in 0.5 mL | <34 | 6,000 | 0.20 | 0.30 |
35–41 | 7,000 | 0.15 | 0.35 | |
42–46 | 8,000 | 0.10 | 0.40 | |
47–51 | 9,000 | 0.05 | 0.45 | |
52–57 | 10,000 | None | 0.50 | |
14,000 IU in 0.7 mL | 58–63 | 11,000 | 0.15 | 0.55 |
64–67 | 12,000 | 0.10 | 0.60 | |
68–72 | 13,000 | 0.05 | 0.65 | |
73–77 | 14,000 | None | 0.70 | |
18,000 IU in 0.9 mL | 78–83 | 15,000 | 0.15 | 0.75 |
84–88 | 16,000 | 0.10 | 0.80 | |
89–93 | 17,000 | 0.05 | 0.85 | |
94–103 | 18,000 | None | 0.90 | |
2 × 10,000 IU in 0.5 mL | 104–124 | 20,000 | None |
2 × 0.5 |
1 × 10,000 IU in 0.5 mL and 1 × 14,000 IU in 0.7 mL | 125–145 | 24,000 | None |
1 × 0.5 and 1 × 0.7 |
2 × 14,000 IU in 0.7 mL | 146–165 | 28,000 | None |
2 × 0.7 |
1 × 14,000 IU in 0.7 mL and 1 × 18,000 IU in 0.9 mL | 166–183 | 32,000 | None |
1 × 0.7 and 1 × 0.9 |