A secondary objective was added to assess the need to add immunosuppressive treatment to the patient's treatment. As a consequence, it was also to assess the administration of mycofelonate, azathioprine and cyclophosphamide, azathioprine and cyclophosphamide. The inclusion criteria were modified from a single, overly broad and confusing criterion, to four clearly defined criteria. In this In this sense, one of the criteria for withdrawal from the study was also clarified and some more criteria related to the appearance of neoplasms in the patients or the loss of follow-up due to failure to attend scheduled visits. A change was made to the glucocorticoid regimen to be administered in conjunction with rituximab. The need to use antimalarials during treatment was also introduced. In relation to the safety assessment, was include the different evaluations to be carried out in order to assess the safety profile of rituximab in these patients. These assessments included ECG, vital signs and laboratory tests. With regard to the safety section, this was completed with the information provided by the "Information guide on the safety of rituximab" received from the AEMPS.

A modification was made to the wording of the main objective of the study, making it clearer. Likewise, secondary objectives that were already implicitly included in the development of the study were eliminated. As a consequence of the modifications made to the objectives, some changes were made to certain variables of the study. In addition to the changes in objectives and variables, minor modifications were made to the study design, with patients who had not received rituximab in the previous year being recruited instead of in the 2 years prior to inclusion in the study. Another change in the study design was the elimination of the initial cycles of cyclophosphamide administered together with rituximab. Some inclusion criteria were also modified. On the one hand, the above-mentioned change in prior rituximab treatment was modified, and on the other hand, the length of time that potentially fertile patients should use contraception was modified. In relation to the study design and the concomitant medication to be administered during rituximab infusions, the schedule of glucocorticoids to be administered with each rituximab infusion was modified. Likewise, the immunosuppressive regimen to be administered in case of non-response to treatment was also changed. Finally, various laboratory tests were added.

In relation to the definition of complete response included among the study variables, some of the elements that make up the definition of complete response were modified, the most relevant change being the replacement of the assessment of serum creatinine level by the glomerular filtration rate. Related to this change in the assessment parameter, a change was made in one of the items that make up the definition of partial response, taking into account glomerular filtration rate instead of serum creatinine level. The assessment of Selena-sledai response was introduced as a secondary endpoint. In addition, partial and complete response rate at 12, 18 and 24 months was added as a secondary variable. In relation to the selection criteria, there was a modification in them, taking into account the diagnosis by renal biopsy in the 24 weeks prior to inclusion in the study and discarding those patients whose renal biopsy showed interstitial fibrosis/tubular atrophy and/or glomerular sclerosis greater than 50%. In relation to concomitant treatments, the antiproteinuric drugs and the regimen with which they are administered are modified. The latest changes are related to an update of the study's procedural schedule.

This version clarified the withdrawal criterion related to loss to follow-up. To this end, the number of visits the patient should not attend in order to be considered as a loss to follow-up was specified. In relation to visits, the window period in which visits can take place was specified. Finally, the serious adverse event reporting form was eliminated as a specific form was designed for the study.

A modification was made to the primary study criteria by extending the time periods to be taken into account for the assessment of efficacy in obtaining remission. The first exclusion criterion was modified to adapt it to the patients assessed in routine clinical practice. To this end, the restriction that patients had been treated with cyclophosphamide and mycofelonate was eliminated, and patients who had received at least one of the treatments could be included. Likewise, exclusion criterion 6 was modified to exclude prophylactic treatments. Data collection on the need for methotrexate treatment was added to the secondary variables.