EGF + GHRP6 combination therapy reduces disability and mortality in severe acute ischemic stroke patients
Background
Acute ischemic stroke remains a leading cause of disability and death, with current treatments like thrombolysis and thrombectomy having narrow therapeutic windows and limited efficacy in severe cases. There's a critical need for neuroprotective strategies that can extend the treatment window and improve outcomes. Epidermal Growth Factor (EGF) and Growth Hormone Releasing Peptide-6 (GHRP6) have shown promise in preclinical models and early clinical trials for their neuroprotective and regenerative properties, making their combined therapy a compelling candidate to address this unmet need in brain injury recovery.
Study Design
The COURAGE-2 study was a multicenter, open-label, randomized phase III clinical trial. Patients with acute ischemic stroke (NIHSS score 5-20) were enrolled within 12 hours of symptom onset. Participants were randomized to receive either combined therapy (n=95) or standard care (n=93). The intervention group received EGF (75µg) + GHRP6 (5mg) intravenously, twice daily for 7 days. The primary endpoint assessed safety and efficacy at 3 and 6 months using the modified Rankin Scale (mRS). Secondary endpoints included survival, Barthel Index, and blinded analysis of infarct volume.
Results
The study included 188 patients (mean age 63.5±11.3 years, 110 men) with a baseline NIHSS score of 9.5 (95%CI: 8.9-10). The primary endpoint, overall disability improvement at six months, was not met for the intention-to-treat population, showing no significant differences in mRS, Barthel Index, or survival. However, a crucial finding emerged in the severe-stroke subpopulation (baseline NIHSS≥15, n=27):
Treated patients with severe stroke showed significantly reduced disability (mRS at 6 months = 2.6, 95%CI: 1.3-3.8 vs Control 4.7, 95%CI: 2.6-6; p=0.03). This severe-stroke subgroup also demonstrated a reduced mortality risk (HR=0.18, 95%CI: 0.03-0.96; p=0.045). Furthermore, in the middle cerebral artery territory, treated patients experienced greater infarct volume reduction at 30 days (p=0.041). Severe adverse events occurred in 48/188 patients, with 30/95 in the treated group (OR=1.92; 95%CI: 0.981-3.767), but none were deemed treatment-related.
Key Findings
- EGF + GHRP6 therapy missed the primary endpoint for overall disability improvement in the intention-to-treat population.
- In severe stroke (NIHSS≥15, n=27), treated patients had reduced disability (mRS 6-months = 2.6 vs Control 4.7; p=0.03).
- Severe stroke patients receiving EGF + GHRP6 showed reduced mortality risk (HR=0.18; p=0.045).
- Treated patients in the middle cerebral artery territory had greater infarct volume reduction (30 days; p=0.041).
- No treatment-related severe adverse events were reported among 48/188 patients experiencing SAEs.
Why It Matters
This study, despite missing its primary endpoint, provides compelling evidence that EGF + GHRP6 combination therapy could be a valuable neuroprotective strategy specifically for patients suffering from moderate-to-severe acute ischemic stroke. For this high-risk population, current treatment options are often insufficient, leaving a significant gap in care. The observed reductions in disability and mortality, alongside decreased infarct volume, suggest a targeted benefit that warrants further investigation. This finding could lead to refined protocols, potentially focusing on patients with higher baseline NIHSS scores, offering a new therapeutic avenue where existing interventions fall short. The safety profile, with no treatment-related severe adverse events, supports its potential for clinical translation.
ischemic stroke
egf
ghrp6
neuroprotection
clinical trial
phase 3