Thery 1992.
| Methods | Study design: dose‐finding controlled, randomised trial. Method of randomisation: not stated Concealment of allocation: not blinded for treatment allocation, blinded for outcome assessment. Exclusions post‐randomisation: none. Lost to follow‐up: none. |
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| Participants | Country: France, Setting: hospital. No.: 68: Fraxparine 35, UFH 33 Age: Fraxiparine mean 60.1 (SD 2.9) years, UFH mean 64.2 (SD 2.5) years Sex: Fraxiparine 17 M/18 F, UFH 14 M/19 F Inclusion criteria: adults > 18 years with a recent angiographically proved PE (within 3 days of the onset of symptoms) and with a pulmonary vascular obstruction assessed by the local radiologists between 15% and 55% (index of severity according to Miller 5 to 18) Exclusion criteria: angiographically determined vascular obstruction < 15% or > 55%, any sign of clinical severity defined as shock, acute cor pulmonale or right heart failure, any contraindication to heparin, active peptic ulcer, recent history of cerebrovascular haemorrhage or ischaemia, known bleeding tendency, previous history of heparin‐induced thrombocytopenia, haemorrhagic diathesis, pre‐existing coagulation disorders, severe renal or hepatic dysfunction, severe systemic hypertension, known pericarditis or endocarditis, pregnancy, pre‐existing DVT or PE within 12 months preceding the inclusion or use of thrombolytic agents, heparin at therapeutic doses for more than 48 hours before inclusion, oral anticoagulants, acetylsalicylic acid or ticlopidine during the 7 days before inclusion, any contraindication to isotopic or angiographic investigations and free‐floating inferior vena cava thrombus. |
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| Interventions | Treatment: LMWH: Fraxiparine 400 anti‐factor Xa IU U/kg in 2 daily injections Control: UFH: i.v. bolus injection of 50 IU/kg followed by continuous infusion of an initial dose of 600 IU/kg. Treatment duration: 14 days Oral anticoagulation: none |
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| Outcomes | Primary: pulmonary vascular obstruction Secondary: clinical recurrence of VTE, death and haemorrhagic complications |
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| Notes | Follow‐up: 8 days Before completion of the trial, enrolment in 2 Fraxiparine groups stopped because of a high incidence of major bleedings. Those 2 groups were given Fraxiparine at a high dose of 600 and 900 anti‐factor Xa IU/kg. Data from these groups were not included in the analyses in this review. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Random treatment allocation schedules were prepared for each clinical centre using sealed treatment allocation envelopes". Comment: insufficient information about the sequence generation process to permit judgement of ‘Low risk’ or ‘High risk’. |
| Allocation concealment (selection bias) | Unclear risk | Quote: "Random treatment allocation schedules were prepared for each clinical centre using sealed treatment allocation envelopes". Comment: although the use of assignment envelopes is described, it remains unclear whether envelopes were sequentially numbered and opaque. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not blinded for treatment allocation. Comment: given the clinical outcomes of the study, review authors judged that the non‐blinding of the participants and staff was unlikely to have affected the outcomes. |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "the study could not be performed double‐blind because of the different modes of administration and above all the need for dosage adjustments in the UFH group. However, the main assessment criterion was blindly evaluated by a central independent panel of three radiologists". Comment: review authors judged that the non‐blinding of the participants and staff was unlikely to have affected the outcomes. Furthermore, the blinding of outcome assessment was ensured. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Reasons for losses to follow‐up not clearly stated. |
| Selective reporting (reporting bias) | Low risk | Study reports data on all pre‐specified outcomes. |
| Other bias | Low risk | Study appears to be free from other sources of bias. |
APTT: activated partial thromboplastin time cm: centimetre DVT: deep vein thrombosis F: female INR: International normalised ratio IU: International units i.v.: intravenous kg: kilogram LMWH: low molecular weight heparin M: male mg: milligram mL: millilitre mm: millimetre mmHg: millimetres of mercury NSAID: nonsteroidal anti‐inflammatory drug PE: pulmonary embolism PTE: pulmonary thromboembolism o.d.: once daily s.c.: subcutaneous SD: standard deviation UFH: unfractionated heparin VKA: vitamin K antagonists VTE: venous thromboembolism