INITIATE   AktivRecruiting

Baggrund og rationaleBackground and rationale

Konventionel hæmodialyse tre gange ugentligt har været standardbehandling siden 1970'erne, men opstart af dialyse medfører en betydelig fysisk og psykisk belastning. Observationelle data antyder, at inkremental to-gange-ugentlig hæmodialyse kan være non-inferior i forhold til konventionel tre-gange-ugentlig dialyse, med potentielle fordele i overlevelse, livskvalitet og bevarelse af residual nyrefunktion. Evidens fra randomiserede studier er imidlertid fortsat begrænset. Conventional thrice-weekly hemodialysis has been the standard since the 1970s, yet dialysis initiation imposes substantial physical and psychological burden. Observational data suggest that incremental twice-weekly hemodialysis may be non-inferior to conventional thrice-weekly care, with potential benefits in survival, quality of life, and preservation of residual kidney function. Randomized evidence remains limited.

INITIATE undersøger inden for APT-KIDNEY platformen, om to-gange-ugentlig hæmodialyse er non-inferior til tre-gange-ugentlig for tid til all-cause mortalitet inden for 12 måneder hos incidente dialysepatienter med residual urinproduktion. Within the APT-KIDNEY platform, INITIATE will assess whether twice-weekly hemodialysis is non-inferior to thrice-weekly for time to all-cause mortality within 12 months in incident dialysis patients with residual urine output.

StudiedesignStudy design

Investigator-initieret, pragmatisk, randomiseret, parallel-gruppe, open-label domæne. Fixed-sample frekventistisk design uden adaptive features. Event-driven inklusion med rekruttering, der fortsætter, indtil prædefineret antal primære hændelser er akkumuleret. Forventet inklusionsperiode: ca. 5 år (planlægningsantagelse n = 100 per år). Investigator-initiated, pragmatic, randomized, parallel-group, open-label domain. Fixed-sample frequentist design without adaptive features. Event-driven enrolment continuing until the pre-specified number of primary events is accrued. Anticipated enrolment period: approximately 5 years (planning assumption n = 100/year).

Open-label allokering anvendes, da blinding af dialyseordination ikke er praktisk gennemførligt og ville kræve "dummy"-dialysebehandlinger. EQ-5D-5L indsamles via standardiseret digital selvudfyldelse med neutrale instruktioner og minimal personaleinvolvering for at mindske bias. An open-label design is used because blinding of dialysis prescription is not feasible and would require "dummy" sessions. EQ-5D-5L is collected through standardized digital self-completion with neutral instructions and minimal staff involvement to mitigate bias.

EligibilitetEligibility

InklusionskriterierInclusion criteria

• Opstart af vedligeholdelses-hæmodialyse ≤ 90 dage før screening Initiation of maintenance hemodialysis ≤ 90 days prior to screening
• Residual urinproduktion ≥ 1.000 mL/døgn på timed urinopsamling Residual urine output ≥ 1,000 mL per 24 hours on timed urine collection

Patienter med tidligere mislykket nyretransplantation, der nu er på vedligeholdelses-hæmodialyse, er eligible, hvis alle øvrige kriterier er opfyldt. APT-KIDNEY's kerne-eligibilitetskriterier (alder ≥ 18 år, eligibilitet til ≥ 1 aktivt domæne) gælder. Patients with a previously failed kidney transplant who have transitioned to maintenance hemodialysis are eligible provided all other criteria are met. The APT-KIDNEY core eligibility criteria (age ≥ 18, eligible for ≥ 1 active domain) apply.

EksklusionskriterierExclusion criteria

• Forventet levetid < 3 måneder Life expectancy < 3 months
• Dokumenteret plan for skift i nyreerstatningsterapi inden for 3 måneder (peritonealdialyse, hjemmehæmodialyse, transplantation) Documented plan for shift in kidney replacement therapy within 3 months (peritoneal dialysis, home hemodialysis, transplantation)
• Tidligere peritonealdialyse i mere end 3 måneder Prior peritoneal dialysis for more than 3 months

InterventionerInterventions

Intervention: hæmodialyse to gange ugentligt. Kontrol: hæmodialyse tre gange ugentligt. Randomisering 1:1. Protokoldefinerede tærskelværdier for eskalation til tre-gange-ugentlig dialyse er beskrevet, med endelig beslutning ved klinikerens skøn. Ved sustained crossover (> 4 sammenhængende uger) flyttes deltageren ikke fra ITT-populationen, men markeres for per-protokol sensitivitetsanalyse. Intervention: hemodialysis twice weekly. Control: hemodialysis thrice weekly. 1:1 randomization. Protocol-defined thresholds for escalation to thrice-weekly are provided, with final decisions at clinician discretion. Sustained crossover (> 4 consecutive weeks) does not remove participants from the ITT population but flags them for per-protocol sensitivity analysis.

UdfaldOutcomes

StatistikStatistics

Analyser følger intention-to-treat under en treatment-policy strategi for alle intercurrent events (ICH E9 R1). Non-inferioritet vurderes ved Cox proportional hazards model; konkluderes hvis øvre grænse af det tosidet 95 % konfidensinterval for hazard ratio er ≤ 1,30. EQ-5D-5L sammenlignes ved 12 måneder med understøttende MMRM på tværs af planlagte måletidspunkter. Ingen planlagte efficacy-interim-analyser; prædefinerede IDSMC-sikkerhedsreviews afholdes broadly i takt med event-akkumulation. Analyses follow intention-to-treat under a treatment-policy strategy for all intercurrent events (ICH E9 R1). Non-inferiority is assessed using a Cox proportional hazards model; concluded if the upper bound of the two-sided 95% confidence interval for the hazard ratio is ≤ 1.30. EQ-5D-5L is compared at 12 months with supportive MMRM across scheduled assessments. No planned efficacy interim analyses; pre-specified IDSMC safety reviews are held broadly aligned with event accumulation.

Komplet statistisk analyseplan publiceres som tillæg til domæneprotokollen før database-lås. A complete statistical analysis plan will be published as an appendix to the domain protocol prior to database lock.

DokumenterDocuments