Agnelli 2009.

Study characteristics
Methods	Trial acronym: PROTECHT Design: multicentre, double‐blind, placebo‐controlled trial with modified intention‐to‐treat analysis, including participants who received ≥ 1 dose of study treatment. Median duration of follow‐up: 111 days in nadroparin; 113 days in placebo
Participants	Ambulatory patients aged > 18 years who were receiving chemotherapy for metastatic or locally advanced lung, gastrointestinal, pancreatic, breast, ovarian, or head and neck cancer Mean age: 62.1 (SD 10.3) years in nadroparin group; 63.7 (SD 9.2) years in placebo group Gender, n (%) males: 372 (48.4%) in nadroparin group; 183 (48%) in placebo group Metastatic disease, n (%): not reported Previous VTE, n (%): 12 (1.6%) in nadroparin group; 6 (1.6%) in placebo group
Interventions	Intervention: LMWH, nadroparin 3800 IU SC, once daily Control: placebo Study treatment started on the same day as chemotherapy (the first cycle or a new course), and was given for the duration of chemotherapy or up to a maximum of 120 days (± 10 days).
Outcomes	Primary outcomes: composite of symptomatic venous or arterial thromboembolic events occurring during study treatment plus 10 days; major bleeding that occurred between randomisation and 48 hours after last injection of study drug Secondary efficacy outcomes: incidental thromboembolic events incidentally diagnosed; survival at end of study treatment and at 12 months; superficial venous thrombosis of lower limbs; response to chemotherapy; central venous catheter‐related complications of possible thrombotic origin Secondary safety outcome: minor bleeding
Notes	Antiplatelet agents, oral anticoagulants, fibrinolytic agents, UFH, or LMWH other than nadroparin not allowed during study Funding: Italfarmaco SpA, Milan, Italy Disclosure of potential conflicts of interest: the scientific director of Italfarmaco was involved as an author. Publication format: published as full text
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The randomisation list was generated by an independent statistician who used a standard permuted block of six without stratification. The list was generated with SAS version 8.2." Comment: adequate method of sequence generation.
Allocation concealment (selection bias)	Low risk	Quote: "The allocation sequence was available online to the investigators using the Hypernet web‐based system. At the time the investigator accessed the web‐based system with personal codes (user ID and password) and requested the treatment allocation for a new patient who fulfilled the eligibility criteria, the system assigned the next free number in accordance with the randomisation sequence" Comment: adequate method of allocation concealment.
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "Patients and investigators did not know whether study drug or placebo was being given, since pre‐filled syringes were used which were identical in appearance. Treatment assignments were masked from all study personnel and participants for the duration of the study." "All study outcomes were assessed by a central independent adjudication committee whose members were unaware of patients’ study‐group allocation." Comment: double‐blind RCT and adequate methods of blinding.
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "All randomised patients who received at least one dose of the study treatment were included in the efficacy and safety analyses." Comment: 769/779 (98.7%) participants randomised were analysed in the LMWH group, 381/387 (98.4%) randomised were analysed in the placebo group.
Selective reporting (reporting bias)	Low risk	All outcomes reported in the methods section were addressed in the results or discussion section.