Table 2 List of major protocol amendments

SA01

• Clarification of randomisation target of 154 patients

• All references to Short Form 36 Quality of Life (SF-36 QoL) questionnaire removed

• Added an exclusion criterion: patients must have access to phone for investigator trial contact

• Clarified sample collection and analysis

• Clarified procedure pre-randomisation

• Clarified that patients may also be excluded from randomisation for clinical reasons other than X-ray appearances

• Updated summary tables and clarified pre-randomisation day nomenclature

• Stipulated a time window in which patients must have first indwelling pleural catheter (IPC) drainage post-randomisation

• Clarified time window in which patients may have follow-up appointments

• Clarified wording in safety reporting section and highlighted expected minor side effects from talc

• Updated members of the Trial Steering Committee

• New sites added: Preston, Portsmouth and Bristol Royal Infirmary

SA02

• Change of principal investigator at Portsmouth site

SA03

• New sites added: Worcester, North Staffordshire, North Tyneside, Middlesbrough, South Manchester and Blackpool

• Creation of letter and short trial summary for district nurses

• Alteration to primary endpoint; changing minimal fluid volume required for pleurodesis from 20 to 50 mls

• Change to time limit given to patients to consider patient information sheet

• Removed requirement that trial chest X-ray must only be taken as a posterior-anterior image

• Trial flow chart updated, allowed patients to have follow-up appointments at satellite centres

• Allowance for patients to be approached as an inpatient but management must be as an outpatient for trial

• Clarifications to adverse event and serious adverse event reporting procedures

SA04

• New site added: Bath

SA05

• New sites added: London, Mansfield, Stockton-on-Tees and Sheffield

• Clarification of wording of primary endpoint, removal of duplicate secondary endpoint and addition of new secondary endpoint

• Clarification of definition of trapped lung in trial flow chart and protocol

• Addition of new QoL questionnaire (QLQ-C30) for all new trial participants

• Expanded the use of pleural manometry to all centres

• Removed the need for 0.9% saline placebo to be sourced from a particular manufacturer

• Updated wording of how the primary outcome will be analysed

• Updated membership of the Trial Steering Committee

SA06

• New sites added: Northampton, Ayr, Cambridge, Aintree and Hull

• Change of inclusion criteria to require World Health Organisation (WHO) performance of two or better to be eligible, three if score will decrease to two after drainage.

• Allow patients with previous pleurodesis as long as longer than 56 days before trial entry

• Relax follow-up visits by allowing day 42 and 56 to be carried out over the telephone

• Allow carers or relatives to perform chest drains after the day 28 post-randomisation visit

• Extend recruitment period to May 2015

• Relaxation of manometry recordings from every 100 ml to every 100 to 200 ml

• Updated membership of the Trial Steering Committee