Trial Outcomes & Findings for TRANSFORM - Observational Cohort Study of Darbepoetin Alfa Use in European Union (EU) Hemodialysis Patients Switched From PEG Epoetin Beta (NCT NCT01997892)

NCT ID: NCT01997892

Last Updated: 2014-06-09

Results Overview

Hemoglobin concentration from 3 months prior to switch to darbepoetin alfa until the end of the observation period.

• Recruitment status: COMPLETED
• Target enrollment: 1027 participants
• Primary outcome timeframe: Month -3, -2, -1 (pre-switch), and Month 1, 2, 3, 4, 5 and 6 (post-switch)
• Results posted on: 2014-06-09

Participant Flow

First patient enrolled 28 August 2012; Last patient enrolled 3 July 2013.

Participant milestones

Measure	Chronic Kidney Disease (CKD) Participants with CKD on dialysis and treated with PEGylated (PEG) epoetin beta immediately prior to being switched to darbepoetin alfa.
Overall Study STARTED	1027
Overall Study Received Darbepoetin Alfa	987
Overall Study COMPLETED	959
Overall Study NOT COMPLETED	68

Reasons for withdrawal

Measure	Chronic Kidney Disease (CKD) Participants with CKD on dialysis and treated with PEGylated (PEG) epoetin beta immediately prior to being switched to darbepoetin alfa.
Overall Study Physician Decision	2
Overall Study Lost to Follow-up	6
Overall Study Death	14
Overall Study Renal transplant	8
Overall Study Other	3
Overall Study Study completion data not recorded	35

Baseline Characteristics

TRANSFORM - Observational Cohort Study of Darbepoetin Alfa Use in European Union (EU) Hemodialysis Patients Switched From PEG Epoetin Beta

Baseline characteristics by cohort

Measure	Chronic Kidney Disease (CKD) n=785 Participants Participants with CKD on dialysis and treated with PEG epoetin beta immediately prior to being switched to darbepoetin alfa.
Age, Continuous	68.7 years STANDARD_DEVIATION 14.3 • n=5 Participants
Sex: Female, Male Female	344 Participants n=5 Participants
Sex: Female, Male Male	441 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month -3, -2, -1 (pre-switch), and Month 1, 2, 3, 4, 5 and 6 (post-switch)

Population: Primary analysis set; participants with available data at each time point (indicated by "n").

Hemoglobin concentration from 3 months prior to switch to darbepoetin alfa until the end of the observation period.

Outcome measures

Measure	Chronic Kidney Disease (CKD) n=785 Participants Participants with CKD on dialysis and treated with PEG epoetin beta immediately prior to being switched to darbepoetin alfa.	Post-switch Period From the date of the switch to darbepoetin alfa, until up to 6 months.
Hemoglobin Concentration at Monthly Intervals Month -3 (n=725)	11.27 g/dL Standard Deviation 1.09	—
Hemoglobin Concentration at Monthly Intervals Month -2 (n=766)	11.26 g/dL Standard Deviation 1.08	—
Hemoglobin Concentration at Monthly Intervals Month -1 (n=769)	11.19 g/dL Standard Deviation 1.06	—
Hemoglobin Concentration at Monthly Intervals Month 1 (n=763)	11.14 g/dL Standard Deviation 1.09	—
Hemoglobin Concentration at Monthly Intervals Month 2 (n=755)	11.36 g/dL Standard Deviation 1.13	—
Hemoglobin Concentration at Monthly Intervals Month 3 (n=749)	11.48 g/dL Standard Deviation 1.14	—
Hemoglobin Concentration at Monthly Intervals Month 4 (n=754)	11.38 g/dL Standard Deviation 1.15	—
Hemoglobin Concentration at Monthly Intervals Month 5 (n=739)	11.33 g/dL Standard Deviation 1.15	—
Hemoglobin Concentration at Monthly Intervals Month 6 (n=742)	11.29 g/dL Standard Deviation 1.14	—

SECONDARY outcome

Timeframe: Month -3, Month -2, Month -1

Population: Primary analysis set; participants with available data at each time point (indicated by "n").

Mean weekly doses were calculated per participant by first calculating a mean daily dose for the interval (by dividing each dose evenly between the days bounded by its date of administration and the day before the next dose, then taking a mean of these partial doses for the days in the interval) and multiplying by 7 to convert to a weekly dose. Weekly doses >150 μg have been excluded as they were deemed infeasible values derived by the algorithm.

Outcome measures

Measure	Chronic Kidney Disease (CKD) n=785 Participants Participants with CKD on dialysis and treated with PEG epoetin beta immediately prior to being switched to darbepoetin alfa.	Post-switch Period From the date of the switch to darbepoetin alfa, until up to 6 months.
PEG Epoetin Beta Dose From the Start of the Observation Period Until the Switch Month -3 (n=740)	27.7 μg/week 95% Confidence Interval 23.7 • Interval 26.3 to 29.2	—
PEG Epoetin Beta Dose From the Start of the Observation Period Until the Switch Month -2 (n=779)	26.5 μg/week 95% Confidence Interval 22.1 • Interval 25.2 to 27.9	—
PEG Epoetin Beta Dose From the Start of the Observation Period Until the Switch Month -1 (n=783)	27.4 μg/week 95% Confidence Interval 24.2 • Interval 26.0 to 28.8	—

SECONDARY outcome

Timeframe: Month 1, 2, 3, 4, 5 and 6

Population: Primary analysis set; participants with available data at each time point (as indicated by "n").

Mean weekly doses were calculated per participant by first calculating a mean daily dose for the interval (by dividing each dose evenly between the days bounded by its date of administration and the day before the next dose, then taking a mean of these partial doses for the days in the interval) and multiplying by 7 to convert to a weekly dose. Weekly doses >150 μg have been excluded as they were deemed infeasible values derived by the algorithm.

Outcome measures

Measure	Chronic Kidney Disease (CKD) n=785 Participants Participants with CKD on dialysis and treated with PEG epoetin beta immediately prior to being switched to darbepoetin alfa.	Post-switch Period From the date of the switch to darbepoetin alfa, until up to 6 months.
Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period Month 1 (n=782)	29.4 μg/week 95% Confidence Interval 26.1 • Interval 27.9 to 30.9	—
Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period Month 2 (n=778)	27.8 μg/week 95% Confidence Interval 26.0 • Interval 26.3 to 29.3	—
Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period Month 3 (n=780)	25.4 μg/week 95% Confidence Interval 26.8 • Interval 23.9 to 27.0	—
Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period Month 4 (n=779)	23.3 μg/week 95% Confidence Interval 27.6 • Interval 21.9 to 24.9	—
Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period Month 5 (n=777)	23.8 μg/week 95% Confidence Interval 26.5 • Interval 22.3 to 25.3	—
Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period Month 6 (n=769)	25.6 μg/week 95% Confidence Interval 25.5 • Interval 24.1 to 27.1	—

SECONDARY outcome

Timeframe: Week -1 and Week 1

Population: Primary analysis set

Dose ratio is the average weekly dose of the first darbepoetin alfa dose divided by the average weekly dose of peg-epoetin beta at switch (μg darbepoetin alfa per 1 μg pegylated-epoetin beta).

Outcome measures

Measure	Chronic Kidney Disease (CKD) n=785 Participants Participants with CKD on dialysis and treated with PEG epoetin beta immediately prior to being switched to darbepoetin alfa.	Post-switch Period From the date of the switch to darbepoetin alfa, until up to 6 months.
Dose Ratio Measured at the Time of Switch From PEG Epoetin Beta to Darbepoetin Alfa	1.06 ratio Interval 1.01 to 1.11	—

SECONDARY outcome

Timeframe: Thre months prior to switch and 6 months after the switch

Population: Primary Analysis Set with available data

The hemoglobin rate of change is the maximum monthly increase and maximum monthly decrease for the pre- and post-switch periods. Within each period, the difference was calculated between each hemoglobin value and the most recent hemoglobin value taken at least 28 days previously. The rate of change was calculated by dividing this difference by the number of days in the interval and multiplying by 28. The maximum and minimum rate of change was then determined per participant.

Outcome measures

Measure	Chronic Kidney Disease (CKD) n=774 Participants Participants with CKD on dialysis and treated with PEG epoetin beta immediately prior to being switched to darbepoetin alfa.	Post-switch Period n=785 Participants From the date of the switch to darbepoetin alfa, until up to 6 months.
Hemoglobin Concentration Rate of Change by Period Lowest change during period	-0.73 g/dL/4 week Standard Deviation 0.86	-1.21 g/dL/4 week Standard Deviation 0.88
Hemoglobin Concentration Rate of Change by Period Highest change during period	0.64 g/dL/4 week Standard Deviation 0.71	1.17 g/dL/4 week Standard Deviation 0.74

SECONDARY outcome

Timeframe: Month -3, -2, -1, 1, 2, 3, 4, 5 and 6

Population: Primary analysis set

The percentage of participants with at least one hemoglobin excursion, defined as hemoglobin concentrations below 10.0 g/dL and above 12.0 g/dL during the pre- and post-switch periods.

Outcome measures

Measure	Chronic Kidney Disease (CKD) n=785 Participants Participants with CKD on dialysis and treated with PEG epoetin beta immediately prior to being switched to darbepoetin alfa.	Post-switch Period n=785 Participants From the date of the switch to darbepoetin alfa, until up to 6 months.
Percentage of Participants With Hemoglobin Excursions Month -3	16.8 percentage of participants Interval 14.3 to 19.6	29.0 percentage of participants Interval 25.9 to 32.4
Percentage of Participants With Hemoglobin Excursions Month -2	17.7 percentage of participants Interval 15.1 to 20.6	29.0 percentage of participants Interval 25.9 to 32.4
Percentage of Participants With Hemoglobin Excursions Month -1	15.7 percentage of participants Interval 13.2 to 18.4	24.8 percentage of participants Interval 21.9 to 28.0
Percentage of Participants With Hemoglobin Excursions Month 1	17.8 percentage of participants Interval 15.2 to 20.7	23.1 percentage of participants Interval 20.2 to 26.2
Percentage of Participants With Hemoglobin Excursions Month 2	13.6 percentage of participants Interval 11.3 to 16.2	29.3 percentage of participants Interval 26.1 to 32.6
Percentage of Participants With Hemoglobin Excursions Month 3	11.7 percentage of participants Interval 9.6 to 14.2	33.1 percentage of participants Interval 29.8 to 36.5
Percentage of Participants With Hemoglobin Excursions Month 4	13.8 percentage of participants Interval 11.4 to 16.4	32.6 percentage of participants Interval 29.3 to 36.0
Percentage of Participants With Hemoglobin Excursions Month 5	12.2 percentage of participants Interval 10.0 to 14.7	27.8 percentage of participants Interval 24.7 to 31.0
Percentage of Participants With Hemoglobin Excursions Month 6	14.6 percentage of participants Interval 12.2 to 17.3	26.5 percentage of participants Interval 23.4 to 29.7

Adverse Events

Pre-switch Period

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Post-switch Period

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Pre-switch Period n=987 participants at risk From 3 months prior to the switch until the date of the switch to darbepoetin alfa.	Post-switch Period n=987 participants at risk From the date of the switch to darbepoetin alfa, until up to 6 months.
Vascular disorders Hot flush	0.00% 0/987 • The observation period for individual participants spanned 14 weeks prior to switching from PEG epoetin beta to darbepoetin alfa to a maximum of 26 weeks post-switch. Adverse drug reactions in the Full Analysis Set (all eligible enrolled participants who received at least one dose of darbepoetin alfa) are reported.	0.10% 1/987 • The observation period for individual participants spanned 14 weeks prior to switching from PEG epoetin beta to darbepoetin alfa to a maximum of 26 weeks post-switch. Adverse drug reactions in the Full Analysis Set (all eligible enrolled participants who received at least one dose of darbepoetin alfa) are reported.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results aftercompletion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER