Protocol V2.0 - Change of definition of relapse. The decision to change the definition of relapse was made following widespread consultation with UK Paediatric Nephrologists. Whilst the definition of relapse originally proposed by the International Study of Kidney Disease in Childhood was 3 consecutive days of 2+ proteinuria, in clinical practice this has been replaced by 3 days of 3+ proteinuria. Every major UK Paediatric Nephrology centre uses this latter definition in the day to day management of their patients, and the most recent version of the major international textbook of Paediatric Nephrology also recommends this definition. In practice this makes little difference, as during relapses the large majority of patients rapidly develop very heavy proteinuria which is vastly in excess of both 2+ or 3+ proteinuria. However, we felt that it was important that the study used a definition that was appropriate to clinical practice in 2011. This decision to alter the definition of the primary end point will not impact upon any future decision by the Cochrane group to include the study into their meta-analysis. There are occasions where parents either intentionally or accidentally do not test their child’s urine and relapse is not detected until the child becomes generally oedematous with a very low serum albumin level. This is more often the case in long established cases; in general in the early days parents are anxious and therefore take great care to test their child’s urine on a regular basis. We have, however, decided to expand our definition of relapse to include children with generalised oedema and 3+ or more proteinuria, so that relapse treatment can be commenced straight away, reflecting routine clinical practice. It would be routine for such children to commence immediate relapse treatment rather than waiting for three consecutive days of 3+ proteinuria as the diagnosis of relapse is absolutely clear.

Protocol V2.1 - The protocol has been amended to reflect the Chief Investigator’s title change from a Doctor to Professor. A decision was made by the Chief Investigator to change the time the 10ml blood sample for research purposes could be collected from ‘some point during the first year follow-up’, to ‘anytime during the patient’s follow-up within the trial’. Extension to Recruitment Period - a monitoring meeting took place on 12th Feb 2013 to discuss the progress of the trial with the HTA. In June 2013 recruitment was behind target with 145 patients currently being randomised which was 79 patients below the target of 224 patients for June 2013, despite the number of participating centres being above the original target of 90. A decision was made to request funds to extend the recruitment period to allow the requisite number of patients to be recruited. At the rate of recruitment of 7 patients per month the original target of 224 patients would have been reached by June 2014. The study drop-out rate was also slightly higher than anticipated, with a drop-out rate of 15% rather than the expected 10% drop-out rate. Therefore the recruitment target was increased from 224 to 236 patients to ensure there were 200 analysable patients in total (100 in each arm). At a recruitment rate of 7 patients per month the 236 patients would be recruited by July 2014. We therefore wished to extend the recruitment period by 13 months and to increase the target number of patients to 236. A funding request was submitted to the HTA and approved. The trial should successfully reach its recruitment target of 236 by July 2014, providing the trial with sufficient patients to power the study to reach its research objectives. The protocol has been revised in light of the extended recruitment period and increased participant numbers.

Protocol V2.2 - The protocol was amended to include an extension to the recruitment period from 37 to 40 months. Other minor administrative changes were also made.