Kakkar 2003.

Methods	Study design: multicentre, randomised, open‐label, parallel group comparison trial Method of randomisation: not stated Concealment of allocation: not stated Exclusions post‐randomisation: 54 participants Lost to follow‐up: none
Participants	Country: Spain, Poland and United Kingdom Setting: 27 hospitals No.: 324 participants: 94 bemiparin, 105 bemiparin + VKA, 98 UFH Age: bemiparin mean 63.2 (45.1 to 70.8) years, bemiparin + VKA mean 61.2 (44.4 to 69.5) years, UFH mean 61.2 (49.9 to 70.5) years, Sex: bemiparin 58 M/36 F, bemiparin + VKA 61 M/44 F, UFH 63 M/35 F, Inclusion criteria: people with an acute DVT of the legs, confirmed by venography and who had symptoms for no more than 14 days. Exclusion criteria: people receiving therapeutic doses of heparin or a vitamin K antagonist for more than 48 hours prior to enrolment, clinically symptomatic pulmonary embolism, pregnancy confirmed by urine analysis, ischaemic cerebral vascular accident 1 month prior to enrolment, known cerebral vascular aneurysm, active duodenal ulcer or bacterial endocarditis, severe liver or renal failure, spinal or epidural anaesthesia or lumbar puncture 3 days prior to enrolment, uncontrolled hypertension, allergy to heparin, warfarin, sodium or iodinated contrast medium, history of heparin‐associated thrombocytopenia or platelet count of less than 100,000 platelets per mm³, concurrent treatment with fibrinolytic agents, a body weight of less than 35 kg, treatment with an investigational drug in the last 4 weeks prior to enrolment, inability to attend follow‐up due to geographic inaccessibility and known drug use
Interventions	Treatment 1: 115 anti‐Xa IU per kg of bemiparin as 1 injection every 24 hours based on participants' weight (5000 anti‐Xa for weight < 50 kg, 7,500 anti‐Xa for weight 50 to 70 kg and 10,000 anti‐Xa IU for more than 70 kg) followed by VKA from day 3 10 mg per day for first 3 days then adjusted to achieve an INR between 2 and 3 for 12 weeks Treatment 2: 115 anti‐Xa IU per kg of bemiparin as 1 injection every 24 hours based on participants' weight (5000 anti‐Xa for weight < 50 kg, 7500 anti‐Xa for weight 50 to 70 kg and 10,000 anti‐Xa IU for more than 70 kg) followed by fixed daily dose of 3500 anti‐Xa units for 90 days. Control: i.v. bolus of 5000 UFH followed by a continuous i.v. infusion at a dose of 40,000 IU per 24 hours in participants at low risk of bleeding and 30,000 IU per 24 hours in participants at high risk of bleeding followed by VKA from day 3 10 mg per day for first 3 days then adjusted to achieve an INR between 2 and 3 for 12 weeks. Treatment duration: 12 weeks.
Outcomes	Primary: venographically confirmed change in thrombus size between baseline and day 14 assessed with the use of the Marder score and patency of deep venous system determined by venography or Doppler ultrasound at 12 weeks. Secondary: symptomatic recurrence of DVT and PE, major bleeding (clinically overt and associated with a fall in haemoglobin level of at least 2.0 g per decilitre) and death.
Notes	Follow‐up: 7 days, 14 days, 12 weeks and 28 weeks. In this 3‐armed trial, 2 bemiparin groups were compared with an UFH control group. However, in 1 of the bemiparin groups (treatment 2), participants did not receive concomitant VKA therapy. All other studies included in this review used concomitant VKA therapy and in order for our results to be comparable, data for this group of participants in the Kakkar 2003 study were not included in the analysis.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomly assigned". Comment: insufficient information to permit judgement.
Allocation concealment (selection bias)	Unclear risk	Quote: "Patients were randomly assigned". Comment: insufficient information to permit judgement.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	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	Open label Quote: "The venograms were independently assessed by two radiologists of an independent committee who were unaware of the patients treatment assignments". Comment: outcome assessors were blinded.
Incomplete outcome data (attrition bias) All outcomes	High risk	324 participants in intention‐to‐treat group but only 297 participants included in the per protocol population and only 255 followed up to day 84. Numbers lost to follow‐up not adequately reported.
Selective reporting (reporting bias)	Low risk	Published report includes all expected outcomes.
Other bias	High risk	The study was sponsored by Laboratorios Farmaceuticos Rovi, Madrid, Spain.