Clinical trial NCT03488368: Longterm Renal Oucomes of STOP-IgAN Trial Participants
Official title: Quality Control of STOP-IgAN Trial Results in Longterm Observation With Existing Routine Data of Randomized Trial Participants (STOP-IgAN - Longterm) - Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: IgA Nephropathy
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2018-04-05
Enrollment: 148
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All randomized STOP-IgAN participants with the exception of drop-outs.

Brief summary: IgA nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis in the Western world. Although most IgAN patients take a benign longterm course, about 20-30% progress to end-stage renal disease (ESRD) over 20 years. The majority of current treatment recommendations is based on weak evidence.

In the randomized, controlled Supportive Versus Immunosuppressive Therapy for the Treatment Of Progressive IgAN (STOP-IgAN) trial, the investigators analyzed whether additional immunosuppression on top of standardized supportive care provides renal benefits in patients with progressive IgAN. Patients with persisting proteinuria \>0.75 g/d (n=162) despite optimized supportive treatment including control of blood pressure and proteinuria, were randomized to either continue on supportive care or to receive additional immunosuppression during the 3-year trial phase. It was observed that immunosuppressive therapy in addition to optimized supportive care led to more full clinical remissions, but eventually did not better preserve renal function, did not better save patients from ESRD development and evoked more adverse effects such as infections, weight gain and diabetes.

Aim of this planned study is to analyze renal outcome measures and adverse effects in the longterm observation of all randomized STOP-IgAN participants to ascertain quality and strength of the original trial results. By its observational nature, this quality control study includes the 162 IgAN patients (with the exception of drop-out patients) that had been previously randomized into the original STOP-IgAN trial.

Information on serum creatinine, proteinuria, ESRD, death, relevant adverse events such as major cardiovascular events, osteoporosis, osteonecrosis, bone fractures, diabetes, malignancies and interim treatment will be collected as available from existing routine records until March 31, 2018.

Primary endpoint is the time to the first occurring event of the binary composite of all-cause death, ESRD or decline in estimated glomerular filtration rate (eGFR) by at least 40% as compared to enrollment into the original trial. Secondary outcome measures comprise the individual components of the primary endpoint, absolute eGFR at the end of observation, proteinuria and adverse events. Information on specific treatments with renin-angiotensin-system (RAS)-blocking agents and/or interim immunosuppression will also be collected. All data will be recorded in a pseudonymous fashion in a central electronic data base located at the PI's site.

Detailed description: Aim: Observational quality control study to analyze renal outcome measures and adverse events in the longterm observation of all randomized STOP-IgAN participants to ascertain quality and strength of the original trial results.

Eligible subjects/sample size: By its observational nature, this study includes the 162 IgAN patients (with the exception of drop-out patients) that had been previously randomized into the original STOP-IgAN trial. Since this study is performed as quality control study of previously randomized patients, a new written informed consent is not necessary.

Endpoints: Primary endpoint is the time to the first occurring event of the binary composite of all-cause death, ESRD or decline in estimated glomerular filtration rate (eGFR) by at least 40% as compared to enrollment into the original trial (time-to-event analysis). Secondary outcome measures comprise the individual components of the primary endpoint, absolute eGFR at the end of observation, proteinuria and adverse events. Information on specific treatments with renin-angiotensin-system (RAS)-blocking agents and/or interim immunosuppression will also be collected.

Data collection: Available information on serum creatinine, proteinuria, ESRD, death, relevant adverse events such as major cardiovascular events, osteoporosis, osteonecrosis, bone fractures, diabetes, malignancies and interim treatment will be collected retrospectively as available from existing nephrology routine records until March 31, 2018. The involved nephrology departments (all in Germany) will be contacted by phone and asked to provide these informations from the randomized STOP-IgAN patients. All data will be recorded in a pseudonymous fashion in a central electronic data base located at the PI's site. To assure high-standard data quality, source data entry will be performed in a double-entry mode, i.e. each data point will be entered independently by two individuals.

Eligibility criteria: Inclusion Criteria:

All randomized STOP-IgAN participants.

Exclusion Criteria:

Drop-outs of the main STOP-IgAN trial.

Primary outcomes:
measure: Time to the first occurring event of the binary composite of all-cause death, end-stage renal disease (ESRD) and of estimated glomerular filtration rate (eGFR)-loss >40% based on available data by March 31, 2018.
timeFrame: as available by March 31, 2018
Secondary outcomes:
measure: all-cause death
timeFrame: as available by March 31, 2018
measure: end-stage renal disease (ESRD)
timeFrame: as available by March 31, 2018
measure: first occurrence of eGFR-loss > 40%
timeFrame: as available by March 31, 2018
measure: first occurrence of eGFR-loss > 30%
timeFrame: as available by March 31, 2018
measure: course of proteinuria
timeFrame: as available by March 31, 2018
measure: Occurrence of major adverse cardiovascular events (MACE) and other relevant adverse events
timeFrame: as available by March 31, 2018
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Medical Clinic II, University Hospital Aachen
Study officials:
affiliation: RWTH Aachen University, University Hospital
name: Juergen Floege, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rauen T, Eitner F, Fitzner C, Sommerer C, Zeier M, Otte B, Panzer U, Peters H, Benck U, Mertens PR, Kuhlmann U, Witzke O, Gross O, Vielhauer V, Mann JF, Hilgers RD, Floege J; STOP-IgAN Investigators. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N Engl J Med. 2015 Dec 3;373(23):2225-36. doi: 10.1056/NEJMoa1415463.