Risks and benefits of bisphosphonate use in patients with chronic kidney disease: a population-based cohort study

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/28025
• EU PAS number:
  EUPAS10029
• Study ID:
  28025
• Official title and acronym:
  Risks and benefits of bisphosphonate use in patients with chronic kidney disease: a population-based cohort study
• DARWIN EU® study:
  No
• Study countries:
  Denmark

  United Kingdom
• Study description:
  AIMS: We aim to study, in chronic kidney disease (CKD) patients, the association between oral bisphosphonate (BP) use and:1.CKD progression (WP1), 2.fracture risk (WP2), 3.hypocalcemia/hypophosphoatemia and adverse events (WP3), and 4.bone mineral density (BMD)(WP4).DESIGN: Population-based cohort studies using routinely collected data.POPULATION: Participants aged 40 years or older, with CKD stage 3B or above (eGFR<45ml/min/1.73m2). Previous users of anti-osteoporosis medications and those with <2 years follow-up data available will be excluded.OUTCOMES: For WP1: CKD progression based on stage progression or requirement ofhaemodialysis/transplantation (primary outcome) and change in eGFR (secondary outcome). WP2: READ/OXMIS(CPRD) codes will be used to ascertain osteoporotic (all but face/skull/fingers/toes) fracture/s. WP3: ICD10/OPCS codes(HES) will be used to identify:1.acute kidney injury, 2.hospitalization for hypocalcemia/hypophosphataemia, and 3.upper gastro-intestinal events. WP4: annualized hip BMD % change.SAMPLE SIZE: According to feasibility counts from CPRD, the number of eligible participants is of 204,528, with 34,127 being BP users. These numbers would provide 90% power to detect as significant a =15% fracture reduction, a =10% increase in CKD progression and a =20% excess risk of adverse events associated with BP use. The Danish database includes >35,000 patients. We expect to identify at least 500 CKD patients defined as BP users matched 1:5 to 2,000 non-users, which would provide >80% power to detect as significant a >25% bone loss reduction.STATISTICAL ANALYSES: BP use will be introduced as a time-varying exposure. Cox regression stratified by propensity matched sets will be used to estimate the association between BP use and the study outcomes(WP1/2/3). Linear regression models will be fitted to study the association between BP use and hip BMD in CKD patients(WP4).
• Study status:
  Finalised

Research institutions and networks

Institutions

National Perinatal Epidemiology Unit (NPEU), University of Oxford

United Kingdom

NA (database study]

Study timelines

Date when funding contract was signed

Actual: 25/03/2015

Study start date

Planned: 01/03/2016

Actual: 01/03/2016

Data analysis start date

Planned: 01/09/2016

Actual: 01/09/2016

Date of interim report, if expected

Planned: 30/11/2016

Actual: 30/11/2016

Date of final study report

Planned: 14/09/2018

Actual: 30/09/2018

Sources of funding

Other

More details on funding

NIHR, University of Oxford

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Non-EU RMP only