Alfuzosin Proposal

Proposed Title

Real-World Comparative Safety Evaluation of a Newer Optimized-PK Alfuzosin Formulation Versus Traditional Alfuzosin in Indian Men With LUTS: A Retrospective EMR-Based Study

Study Rationale

Benign Prostatic Hyperplasia (BPH) associated Lower Urinary Tract Symptoms (LUTS) significantly impact quality of life in aging men. α-blockers, including Alfuzosin, remain a cornerstone of pharmacologic management due to their efficacy in symptom relief. However, traditional Alfuzosin formulations (mainly the Immediate release version) are associated with adverse events such as dizziness and orthostatic hypotension, largely attributable to high peak plasma concentrations.

These adverse events can:

Compromise treatment tolerability
Increase fall and syncope risk, particularly in elderly patients and those with cardiovascular comorbidities
Lead to treatment discontinuation and downstream healthcare utilization

Newer Alfuzosin prolonged release formulations with optimized pharmacokinetic (PK) profiles and controlled drug release reduce peak-related adverse effects while preserving therapeutic efficacy.

A newer Alfuzosin formulation is designed to deliver a more consistent plasma concentration, potentially lowering the incidence of dizziness and clinically significant hypotension in real-world use.

Given limited head-to-head randomized data in Indian patients, real-world evidence (RWE) from Electronic Medical Records (EMR) offers a pragmatic and clinically relevant approach to evaluate comparative safety outcomes in routine practice.

Study Objectives

Primary Objective

To demonstrate that new Alfuzosin formulation is associated with a lower incidence of clinically significant dizziness and orthostatic hypotension compared with traditional Alfuzosin formulations in Indian men with LUTS, using retrospective EMR data.

Secondary Objectives

To compare rates of:
- Falls and syncope
- Emergency room (ER) visits
- Hospitalizations related to hypotension or falls
- Treatment discontinuation or switching
To evaluate safety outcomes in key subgroups:
- Elderly patients (≥65 years)
- Patients with cardiovascular comorbidities (hypertension, diabetes, ischemic heart disease)
- Patients on concomitant antihypertensives

Study Design

Retrospective, Observational Cohort Study

Data Source: De-identified EMR from Indian Hospitals/Healthcare Networks

Study Period: Past 12 months (Index Period)

Follow-up: Minimum 6 months

Setting: Multi-center (Tertiary care hospitals & large urology practices)

Data Sources

💊

Prescription Data

💓

Vital Signs

(Blood Pressure Readings)

📝

Clinical Notes

🏥

Diagnosis Codes

🚑

ER & Hospitalization Records

Study Population

Inclusion Criteria	Exclusion Criteria
Male patients aged ≥45 years Diagnosis of LUTS/BPH Initiated treatment with: Alfuzosin (newer formulation) OR Traditional Alfuzosin formulation First prescription within the last 12 months Minimum of 6 months of follow-up data available	Prior α-blocker use within 3 months before index date History of severe autonomic dysfunction Missing baseline blood pressure data

Exposure Groups

Index Date: Date of first prescription of Alfoo Advance or traditional Alfuzosin

Cohort A

New prolonged release formulation of Alfuzosin

600-900 records

Cohort B

Traditional Alfuzosin formulation

400-600 records

Outcomes

Primary Outcome	Secondary Outcomes
Clinically significant dizziness or orthostatic hypotension, defined as: Documented symptomatic dizziness AND/OR ≥20 mmHg drop in systolic blood pressure upon standing Occurring within 6 months of treatment initiation	Falls or syncope events ER visits related to hypotension, dizziness, or falls Hospitalizations for cardiovascular or fall-related causes Treatment discontinuation or switching Safety outcomes in patients with comorbid conditions

Expected Impact

Generates India-specific real-world evidence on safety advantages of optimized-PK Alfuzosin
Supports clinicians in selecting better-tolerated therapy for LUTS/BPH
Provides regulatory, medical, and commercial evidence aligned with real-world practice
Informs future prospective or pragmatic studies

Key Challenges & Mitigation

Key Challenges

Capturing sufficient patients on traditional Alfuzosin formulations may be challenging due to:

Declining use of immediate-release or older formulations in favor of newer PR/optimized versions
Variability in parameter documentation in prescriptions across hospitals and practice settings

Mitigation Strategies

Conduct a structured pre-study feasibility assessment across shortlisted centers to quantify the availability of traditional Alfuzosin prescriptions within the defined time window.
Prioritize inclusion of high-volume urology centers and hospitals with longer historical prescribing continuity, where traditional formulations may still be in use.
Expand the number of participating centers, if required, to achieve the minimum comparator sample size.
Implement standardized data collection forms to screening and completeness of parameters required in the prescription.
Data quality checks and validation rules during the data-cleaning phase to ensure consistency across sites.

Timeline

Feasibility & Site Selection

EMR capability check, formulation identification, BP data availability

4–6 weeks

Ethics & Data Governance

EC approvals / waivers, data-sharing agreements

4–8 weeks (parallel)

Data Extraction

Cohort identification, data pull, de-identification

4–6 weeks

Data Cleaning & Validation

Missing data checks, formulation mapping, consistency review

3–4 weeks

Analysis & Interpretation

Primary/secondary analyses, sensitivity analyses

4 weeks

Medical Review & Reporting

Executive summary, medical deck, internal sign-off