Table 2 Protocol revision chronology

Original version, 22.02.2011

Amendment Number 1:

Primary reason for amendment:

Changes in the methods sections - a decision to allow the pharmacy at OUH to generate randomization code was made.

Version 2, 18.05.2011

Amendment Number 2:

Primary reason for amendment:

At the request of GCP changes in the ethics section to elaborate on the procedure for obtaining consent.

Version 3, 18.07.2012

Amendment Number 3:

Primary reason for amendment:

The methods section was amended to include a description of the conduct of CRRT during the trial.

Version 4, 25.08.2012

Amendment Number 4:

Primary reason for amendment:

Fleming-Harrington-O’Brien stopping rule and futility measure via ’conditional power’ calculation was introduced.

Version 5, 31.08.2012

Amendment Number 5:

Version 5 was the first version to be submitted to the Danish Health and Medicines Authority and the Danish national scientific ethical committee.

Primary reason for amendment:

The comparator dose which was unconfirmed until this point was included in this new protocol version.

At the request of Danish Health and Medicines Authority changes were made to the exclusion criteria so that patients with chronic renal failure or acute-on-chronic renal failure were ineligible. The methods section was also updated to indicate that a patient who changed from CRRT to intermittent hemodialysis would have reached the end of the study period. In addition, further details about the reporting of adverse events were included.

Version 6, 21.01.2013

Amendment Number 6:

Primary reason for amendment:

At the request of the Danish national scientific ethical committee a separate information sheet for the designated surrogates was developed.

The methods section was also revised due to the acquisition of new dialysis machines at OUH.

Version 7, 06.06.2013

Amendment Number 7:

Primary reason for amendment:

A change in the exclusion criteria:

platelet count of <75× 109/l, changed to <50 × 109/l and INR or APTT ≥1½ times the upper limit of normal changed to ≥2 times the upper limit of normal.