Efficacy and Safety of Entacapone Combined With Madopar in the Treatment of Early Parkinson's Disease: An Observational, Multicenter, Case-Control Study

This is an observational, multicenter, case-control study designed to evaluate the efficacy and safety of Entacapone combined with Madopar (Levodopa/Benserazide, LB) in the treatment of early-stage Parkinson's disease (PD) in Chinese patients. The study is conducted across multiple centers in China and includes patients diagnosed with PD according to the MDS criteria, aged 18-80 years, with a modified Hoehn-Yahr stage of 1-2.5. Participants will be divided into two groups based on their actual clinical treatment: (1) the LBE group (Levodopa/Benserazide/Entacapone) and (2) the LB group (Levodopa/Benserazide only). The study does not involve any randomization, blinding, or intervention allocation; instead, it reflects real-world clinical practice, where all treatment decisions are made solely by the attending physician.

The study will observe patients over a 24-week period to compare the effectiveness of the two treatment strategies in improving motor symptoms, daily living activities, and quality of life, as well as the incidence of adverse events. The primary outcome measure is the change in MDS-UPDRS Part III (motor examination) score from baseline to Week 24. Secondary outcomes include changes in MDS-UPDRS Part II (activities of daily living), Part IV (motor complications), total MDS-UPDRS II+III scores, PDQ-39 quality of life scores, Clinical Global Impression (CGI) scores, MMSE cognitive scores, and modified Hoehn-Yahr staging. Safety assessments include adverse events, serious adverse events, vital signs, laboratory tests, and ECG findings.

All treatments, including medication selection, dosage, and adjustment, will follow the treating physician's routine clinical judgment, and no intervention or modification by the study team will occur. Concomitant medications such as amantadine, anticholinergics, dopamine agonists, and MAO-B inhibitors (e.g., selegiline, rasagiline) are allowed if their doses are stable for at least 30 days before enrollment and remain unchanged throughout the study period.

The estimated sample size is 216 participants, with approximately 108 in each group, allowing for a 10% dropout rate. The study is expected to start in June 2025 and complete by April 2027, with final data analysis by June 2027. The results of this study aim to provide real-world evidence regarding the potential benefits and safety of Entacapone combined with Madopar in the early-stage PD population in China.

Inclusion criteria

Age between 18 and 80 years;

Diagnosed with Parkinson's Disease based on the MDS criteria, confirmed by a movement disorder neurologist;

Modified Hoehn and Yahr stage between 1 and 2.5;

No prior use of entacapone;

MMSE score ≥ 26;

BDI (Beck Depression Inventory) score < 15;

Either:

Has never used levodopa before, or

Has been on a stable dose of levodopa (300-600 mg/day) for at least 1 month prior to enrollment;

Stable doses of amantadine, anticholinergics, dopamine agonists, selegiline, or rasagiline are allowed if maintained for at least 30 days prior to and during the study;

Willing and able to give informed consent and comply with study procedures, with caregiver support if needed.

Exclusion criteria

Previous use of entacapone or tolcapone for more than 30 days, or within 4 weeks before baseline;

Use of dopamine agonists within 4 weeks before baseline;

BDI score ≥ 15;

MMSE score < 26;

Unstable levodopa dosage;

History of dyskinesia;

Diagnosis of atypical or secondary parkinsonism, or history of PD-related neurosurgery;

Clinically significant medical conditions within the past 5 years that could interfere with study participation;

Use of medications known to induce parkinsonism;

Participation in other investigational drug trials within 30 days before baseline.