Study identification

PURI

https://redirect.ema.europa.eu/resource/1000000386

EU PAS number

EUPAS1000000386

Study ID

1000000386

Official title and acronym

Asymptomatic hyperuricemia: to treat or not to treat. A target trial emulation to assess major cardiorenal outcomes (HYPER-TTE-HARV)

DARWIN EU® study

No

Study countries

Spain
United States

Study description

Hyperuricemia is defined as a serum uric acid level >6.8 mg/dl. Most of the uric acid is produced endogenously while the remaining accounts for the metabolism of dietary purines and sugars. Uric acid is mainly excreted by the kidneys and fewer by the intestines. However, certain aspects of the pathophysiology of uric acid are still not clearly understood. In particular, whether elevated uric acid plays a role in the development of cardiovascular risk factors, such as diabetes or hypertension, or the initiation and progression of chronic kidney disease, are still subjects of debate. Cross-sectional studies showed an association between hyperuricemia and chronic kidney disease, but such study design fails to establish the direction of causality. In longitudinal studies, hyperuricemia was associated with an increased risk of incident chronic kidney disease rather than with a risk for progression to end-stage renal disease. Despite this, recent guidelines advocate for not to treat asymptomatic hyperuricemia as many patients do not present related symptoms as gout flares, and urate-lowering drugs are not absent of serious risks. Three large randomized clinical trials found no benefit of allopurinol in slowing kidney disease progression or prevention of cardiovascular events among asymptomatic subjects, but they included patients with normal uric acid levels so that precluded to test our hypothesis. When it comes to real-world, some physicians decide to prescribe urate-lowering drugs for asymptomatic hyperuricemia while others do not. Observational studies provide information on the effectiveness of treatments when randomized trials are not possible. However, making causal inferences are challenging due to lack of randomization and wrong study designs. To overcome this, the target trial emulation provides the framework to avoid bias by designing the hypothetical randomized experiment to answer the specific question of interest using real-world data and appropriate methods

Study status

Ongoing
Research institutions and networks

Institutions

Universidad de Alcalá
Harvard T.H. Chan School of Public Health

Contact details

Antonio Rodriguez Miguel

Primary lead investigator
ORCID number:
0000-0003-0799-1612
Study timelines

Date when funding contract was signed

Planned:

Study start date

Planned:
Actual:

Data analysis start date

Planned:

Date of final study report

Planned:
Sources of funding
Non-EU institutional research programme

More details on funding

The Real Colegio Complutense at Harvard has awarded the principal investigator with a faculty fellowship for research stays at CAUSALab (Harvard T.H. Chan School of Public Health)
Study protocol
Initial protocol

BIFAP_study_protocol_V2_Clean.pdf

English (391.2 KB - PDF)View document
Regulatory

Was the study required by a regulatory body?

No

Is the study required by a Risk Management Plan (RMP)?

Not applicable