Table 3: Open in new tab Trial...

		Double-blind treatment
Visit	1	2	3	4	5	6	7–12…	EoS or EET^e
Month	−0.5	0	0.5	3	6	12	Every 6 months
Time window	−48 days		±14 days	±14 days	±28 days	±28 days	±28 days
Informed consent^a	x
Randomization		x
Significant medical history	x
Physical examination	x	x^h	x^h	x^h	x^h	x^h	x^h	x^h
Serum or urine pregnancy test^b	x	x^b	x^b	x^b	x^b	x^b	x^b	x^b
Blood sampling^f	x	x	x	x	x	x	x	x
Early morning void urine sample^g	x	x		x	x	x	x	x
24-hour urine collection^d–g		x^a		x	x	x	x	x
Residual kidney function^d		x			x	x	x	x
Kt/V per week^d		x			x	x	x	x
Vital signs^j	x	x	x	x	x	x	x	x
EQ-5D and SF-12 questionnaires		x			x	x	xⁱ	x
Biobanking (plasma and urine)		x		x				x
Endpoint assessment^c			x	x	x	x	x	x
Dispense study medication		x		x	x	x	x
Drug accountability (pill count)			x	x	x	x	x	x
SAEs and AESIs		x	x	x	x	x	x	x
Review medications	x	x	x	x	x	x	x	x
Cardiac MRI^k		x				x
Cardiac echocardiography^l		x			x	xⁿ
Body composition measurement^l,m		x			x	xⁿ
Additional biobanking (blood, urine and peritoneal effluent)^l		x			x	xⁿ
Peritoneal dialysis modality, average ultrafiltration 4 weeks prior to study visit and PET data^l,o		x			x	xⁿ	xⁿ	xⁿ
6-minute walking test^l,m		x			x	xⁿ
Kansas City Cardiomyopathy Questionnaire^l		x			x	xⁿ
SDMT		x			x	x	xⁱ	x

		Double-blind treatment
Visit	1	2	3	4	5	6	7–12…	EoS or EET^e
Month	−0.5	0	0.5	3	6	12	Every 6 months
Time window	−48 days		±14 days	±14 days	±28 days	±28 days	±28 days
Informed consent^a	x
Randomization		x
Significant medical history	x
Physical examination	x	x^h	x^h	x^h	x^h	x^h	x^h	x^h
Serum or urine pregnancy test^b	x	x^b	x^b	x^b	x^b	x^b	x^b	x^b
Blood sampling^f	x	x	x	x	x	x	x	x
Early morning void urine sample^g	x	x		x	x	x	x	x
24-hour urine collection^d–g		x^a		x	x	x	x	x
Residual kidney function^d		x			x	x	x	x
Kt/V per week^d		x			x	x	x	x
Vital signs^j	x	x	x	x	x	x	x	x
EQ-5D and SF-12 questionnaires		x			x	x	xⁱ	x
Biobanking (plasma and urine)		x		x				x
Endpoint assessment^c			x	x	x	x	x	x
Dispense study medication		x		x	x	x	x
Drug accountability (pill count)			x	x	x	x	x	x
SAEs and AESIs		x	x	x	x	x	x	x
Review medications	x	x	x	x	x	x	x	x
Cardiac MRI^k		x				x
Cardiac echocardiography^l		x			x	xⁿ
Body composition measurement^l,m		x			x	xⁿ
Additional biobanking (blood, urine and peritoneal effluent)^l		x			x	xⁿ
Peritoneal dialysis modality, average ultrafiltration 4 weeks prior to study visit and PET data^l,o		x			x	xⁿ	xⁿ	xⁿ
6-minute walking test^l,m		x			x	xⁿ
Kansas City Cardiomyopathy Questionnaire^l		x			x	xⁿ
SDMT		x			x	x	xⁱ	x

Table 3:

Trial procedures.

		Double-blind treatment
Procedure	Screening	Baseline						Study close-out visit
Visit	1	2	3	4	5	6	7–12…	EoS or EET^e
Month	−0.5	0	0.5	3	6	12	Every 6 months
Time window	−48 days		±14 days	±14 days	±28 days	±28 days	±28 days
Informed consent^a	x
Randomization		x
Significant medical history	x
Physical examination	x	x^h	x^h	x^h	x^h	x^h	x^h	x^h
Serum or urine pregnancy test^b	x	x^b	x^b	x^b	x^b	x^b	x^b	x^b
Blood sampling^f	x	x	x	x	x	x	x	x
Early morning void urine sample^g	x	x		x	x	x	x	x
24-hour urine collection^d–g		x^a		x	x	x	x	x
Residual kidney function^d		x			x	x	x	x
Kt/V per week^d		x			x	x	x	x
Vital signs^j	x	x	x	x	x	x	x	x
EQ-5D and SF-12 questionnaires		x			x	x	xⁱ	x
Biobanking (plasma and urine)		x		x				x
Endpoint assessment^c			x	x	x	x	x	x
Dispense study medication		x		x	x	x	x
Drug accountability (pill count)			x	x	x	x	x	x
SAEs and AESIs		x	x	x	x	x	x	x
Review medications	x	x	x	x	x	x	x	x
Cardiac MRI^k		x				x
Cardiac echocardiography^l		x			x	xⁿ
Body composition measurement^l,m		x			x	xⁿ
Additional biobanking (blood, urine and peritoneal effluent)^l		x			x	xⁿ
Peritoneal dialysis modality, average ultrafiltration 4 weeks prior to study visit and PET data^l,o		x			x	xⁿ	xⁿ	xⁿ
6-minute walking test^l,m		x			x	xⁿ
Kansas City Cardiomyopathy Questionnaire^l		x			x	xⁿ
SDMT		x			x	x	xⁱ	x

		Double-blind treatment
Procedure	Screening	Baseline						Study close-out visit
Visit	1	2	3	4	5	6	7–12…	EoS or EET^e
Month	−0.5	0	0.5	3	6	12	Every 6 months
Time window	−48 days		±14 days	±14 days	±28 days	±28 days	±28 days
Informed consent^a	x
Randomization		x
Significant medical history	x
Physical examination	x	x^h	x^h	x^h	x^h	x^h	x^h	x^h
Serum or urine pregnancy test^b	x	x^b	x^b	x^b	x^b	x^b	x^b	x^b
Blood sampling^f	x	x	x	x	x	x	x	x
Early morning void urine sample^g	x	x		x	x	x	x	x
24-hour urine collection^d–g		x^a		x	x	x	x	x
Residual kidney function^d		x			x	x	x	x
Kt/V per week^d		x			x	x	x	x
Vital signs^j	x	x	x	x	x	x	x	x
EQ-5D and SF-12 questionnaires		x			x	x	xⁱ	x
Biobanking (plasma and urine)		x		x				x
Endpoint assessment^c			x	x	x	x	x	x
Dispense study medication		x		x	x	x	x
Drug accountability (pill count)			x	x	x	x	x	x
SAEs and AESIs		x	x	x	x	x	x	x
Review medications	x	x	x	x	x	x	x	x
Cardiac MRI^k		x				x
Cardiac echocardiography^l		x			x	xⁿ
Body composition measurement^l,m		x			x	xⁿ
Additional biobanking (blood, urine and peritoneal effluent)^l		x			x	xⁿ
Peritoneal dialysis modality, average ultrafiltration 4 weeks prior to study visit and PET data^l,o		x			x	xⁿ	xⁿ	xⁿ
6-minute walking test^l,m		x			x	xⁿ
Kansas City Cardiomyopathy Questionnaire^l		x			x	xⁿ
SDMT		x			x	x	xⁱ	x

Informed consent is obtained before any study specific procedure is done.

WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/l or equivalent units of HCG) at screening or if pregnancy is suspected.

At each visit the study sites will collect information about primary, secondary and exploratory endpoints.

24-hour diuresis, residual kidney function and Kt/V only recorded in dialysis patients. The most recent Kt/V values for each visit will be recorded with a time window of ±6 months.

EoS: end of study; EET: early end of treatment. EET follow-up visit to be scheduled 14 ± 3 days after discontinuation of study medication.

Visit 1 (screening) and all other visits: sodium, potassium, creatinine and urea; visit 2 (baseline) and EoS/EET: sodium, potassium, creatinine, urea, Hb, HbA1c, cholesterol, HDL cholesterol, LDL cholesterol, calcium, phosphate and PTH.

Assessment of sodium, creatinine and albumin or protein (whichever is available).

Only on indication.

EQ-5D and SF-12 questionnaires and SDMT to be completed once every year after visit 6 until EoS/EET.

Vital signs: heart rate, blood pressure and body weight.

Cardiac MRI substudy only. The MRI will be performed within a time window of ±4 weeks.

Cardiac echocardiography substudy only. The echocardiography, body composition measurement, Kansas City Cardiomyopathy Questionnaire and 6-minute walking test will be performed within a time window of ±4 weeks.

If available on-site.

Only participants who still receive peritoneal dialysis treatment at that time point and participate in the cardiac echography substudy.

Collection of the most recent PET data if performed during routine medical care.

Results of 24-hour urine collection at baseline should be determined within 3 months before the baseline visit. The other 24-hour urine collections should be taken within the time window of the visit.

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