ATTRACT.

Study characteristics
Methods	Multi‐centre, RCT to determine whether PMT prevents PTS in patients with proximal DVT Blinding: single Exclusions post randomisation: 1 Loss to follow‐up: 62 in PCT group, 86 in control group
Participants	Country: 56 clinical centres in the United States Participants: 692 (337 PCT, 355 control) Age (range): 53 (42 ‐ 62) Sex: male and female Inclusion criteria: symptomatic proximal DVT involving the femoral, common femoral, or iliac vein (with or without other involved ipsilateral veins) Exclusion criteria: younger than 16 or older than 75 years of age, were pregnant, had had symptoms for more than 14 days, were at high bleeding risk, had active cancer, had established PTS or had had ipsilateral DVT in the previous 2 years
Interventions	Patients in both groups received initial and long‐term anticoagulant therapy and were provided ECS at the 10‐day follow‐up visit and every 6 months Treatment: "rt‐PA (alteplase (Activase, Genentech) at a dose of <35 mg) was delivered into the thrombus by one of three methods. If the popliteal vein was occluded or the inferior vena cava was involved, physicians were required to use “infusion‐first” therapy, which started with rt‐PA infusion through a multi‐sidehole catheter of the physician's choice for no longer than 30 hours. For the remaining patients, physicians were required to first attempt single‐session thrombus removal with rapid delivery of rt‐PA through the AngioJet Rheolytic Thrombectomy System (Boston Scien‐tific) or the Trellis Peripheral Infusion System (Covidien) and then to infuse rt‐PA for no longer than 24 hours if residual thrombus was present. After the initial delivery of rt‐PA, physicians could use balloon maceration, catheter aspiration, thrombectomy with the use of the AngioJet or Trellis system, percutaneous transluminal balloon venoplasty, stent placement (iliac or common femoral vein), or a combination of procedures to clear residual thrombus and treat obstructive lesions. Stenting was encouraged for lesions that were causing 50% or greater narrowing of the diameter of the vein, robust collateral filling, or a mean pressure gradient of more than 2 mm Hg. Treatment was discontinued when there was at least 90% thrombus removal with restoration of flow or when there was a serious complication.The INR was required to be 1.6 or lower at the start of PMT. During the procedure, patients received twice‐daily sc injections of LMWH in therapeutic doses or UFH infusions (with the dose reduced to 6 to 12 U per kg of body weight per hour (maximum, 1000 U per hour) during rt‐PA infusions). Additional UFH boluses (up to 50 units per kg) were given during the procedure at the physician’s discretion" Control: initial and long‐term anticoagulant therapy and ECS
Outcomes	Primary: development and severity of PTS (defined as a Villalta score of 5 or higher or an ulcer in the leg with the index DVT, at any time between the 6‐month follow‐up visit and the 24‐month follow‐up visit. Patients were also counted as having PTS if they underwent an unplanned endovascular procedure to treat severe venous symptoms) Secondary: Health‐related quality of life Treatment failures that are not PTS Presenting DVT symptoms Degree of resolution of thrombus with PCDT Bleeding Symptomatic PE Symptomatic recurrent DVT Death Trial outcomes were assessed at 10 and 30 days and 6, 12, 18, and 24 months after randomisation
Funding	The trial drug and additional funding were provided by Genentech. Compression stockings were donated by BSN Medical
Declaration of interests	"These companies played no role in the design or conduct of the trial or in the analysis or reporting of the data"
Notes	ClinicalTrials.gov number: NCT00790335
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomization sequence, with varying block sizes, was computer‐generated by an independent statistician"
Allocation concealment (selection bias)	Low risk	"Patients were randomly assigned in a 1:1 ratio to the pharmacomechanical‐thrombolysis group or the control group (no procedural intervention) with the use of a Web‐based central randomization system that ensured concealment of the treatment assignments"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Not possible due to intervention but judged low risk as outcome assessment well described and use of more than one measurement scores
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"The clinical personnel who performed assessments of efficacy outcomes and the adjudicators of safety and efficacy outcomes were unaware of the treatment assignments"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Authors reported detailed descriptions, intention to treat and per protocol outcomes. 80 patients missed all PTS assessments and 52 of these were in the control group (14%), compared to 28 (8%) in the intervention group. Sensitivity analysis carried out by the study authors did not demonstrate a difference in the PTS outcome compared to primary analysis so this was not judged to impact the risk of bias assessment in this domain
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	Within 7 days after randomisation, 5 patients who had been assigned to the control group underwent pharmacomechanical thrombolysis, and 11 patients who had been assigned to the pharmacomechanical thrombolysis group did not undergo the procedure. These patients were clearly reported and excluded from the per‐protocol analysis