Quarles 2003a.

Methods	Study design: parallel RCT Study duration: NS Study follow‐up: 18 weeks
Participants	Country: USA Setting: multicentre (17 centres) Patients ≥ 18 years treated for at least 3 mo with HD and had uncontrolled SHPT (mean PTH ≥ 300 pg/mL, despite availability of standard care (phosphate binders and/or vitamin D sterols)); serum calcium ≥ 8.8 mg/dL and < 11.0 mg/dL; serum phosphorous ≥ 2.5 mg/dL; Ca x P < 70 mg²/dL²; patients receiving vitamin D sterols must have been on a stable dose for at least 21 d before enrolment; dialysis calcium concentration, the dose of any supplements, and the dose of oral phosphate binders must not have been changed during the 7 d before enrolment Number: treatment group (36); control group (35) Mean age ± SD (years): treatment group (49.6 ± 8.5); control group (47.9 ± 14.2) Sex (M/F): treatment group (27/9); control group (17/18) Exclusion criteria: medically unstable; evidence of an active infectious; malignant process; diseases known to cause hypercalcaemia; Hb concentration < 9.0 g/dL or a HCT < 27%; liver transaminases and bilirubin concentrations more than twice the upper limit of normal
Interventions	Treatment group AMG‐073: 25 to 100 mg/d Duration: 12 weeks titration, 6 weeks maintenance Control group Placebo Co‐interventions Treatment group: vitamin D (61%); phosphate binders (100%) Control group: vitamin D (69%); phosphate binders (94%)
Outcomes	Mean reduction in PTH of ≥ 30% during the maintenance phase
Notes	Stop/end point: iPTH reduction = 30% ITT: yes Funding: "Funding for this study was provided by Amgen Inc."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	NS
Allocation concealment (selection bias)	Low risk	Interactive voice‐response system
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	NS
Incomplete outcome data (attrition bias) All outcomes	Low risk	Loss to follow‐up 8.5% of patients
Selective reporting (reporting bias)	High risk	Not reported systematically (end of treatment calcium, phosphorous, PTH and adverse events)
Other bias	High risk	Sponsor on authorship

BSAP ‐ bone‐specific alkaline phosphatase; Ca x P ‐ calcium‐phosphorous product; CAC ‐ coronary artery calcification score; DM ‐ diabetes mellitus; ESKD ‐ end‐stage kidney disease; GFR ‐ glomerular filtration rate; Hb ‐ haemoglobin; HCT ‐ haematocrit; HD ‐ haemodialysis; iPTH ‐ intact parathyroid hormone; ITT ‐ Intention‐to‐treat; MI ‐ myocardial infarction; NA ‐ not available; NS ‐ not stated; NTx ‐ cross‐linked N‐telopeptides of type I collagen; PTH ‐ parathyroid hormone; RCT ‐ randomised controlled trial; SHPT ‐ secondary hyperparathyroidism; TRACP ‐ tartrate‐resistant acid phosphatase