P6305 - NK-1 Receptor Blockade Yields a Promising Boost in Nausea Response Without Added Serious Harm in Gastroparesis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Ashesh Das, MBBS¹, Palwasha Farooqi, MD², Venkata Dileep Kumar Veldi, MBBS³, Emil Vergis Philip, MBBS⁴, Anika Goel, ⁵, Naga Sai Akhil Reddy Gogula, MBBS⁶, Sailesh I S. Kumar, MBBS⁷, Akif Shahid. Khan, MBBS⁸
1KPC Medical College and Hospital , Kolkata, India, Kolkata, West Bengal, India; 2Kabul University of Medical Sciences, Charlotte, NC; 3Gayatri Vidya Parishad Institute of Health care and Medical Technology, Visakhapatnam, Andhra Pradesh, India; 4Madras Medical College, Kottayam, Kerala, India; 5Kakatiya Medical College, Warangal, Warangal, Telangana, India; 6Duke University, Durham, NC; 7Madras medical college, Birmingham, AL; 8Northwest School of Medicine, Nowshera, North-West Frontier, Pakistan

Introduction: Refractory nausea cripples nearly half of gastroparesis patients and remains the symptom least improved by existing prokinetics. Pre-clinical data implicate vagal-afferent NK-1 neuropeptide signaling, yet human evidence has been sparse and fragmented. We therefore synthesized every randomized trial testing NK-1 receptor antagonists in diabetic or idiopathic gastroparesis—a drug class currently licensed only for chemotherapy-induced emesis—to deliver the first aggregate efficacy-and-safety estimate in this population.

Methods: A systematic search of PubMed, Embase, Scopus, and Cochrane Library identified Randomized Controlled Trials (RCTs) that compares the efficacy and safety of drugs blocking NK-1 Receptor for treatment of Diabtetic or idiopathic gastroparesis through May 2025. Data were analysed using RevMan 4.2.1. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using Mantel-Haenszel methods. Random- or fixed-effects models were applied based on heterogeneity (Higgins’ I²). Statistical significance was set at p < 0.05. Risk of bias was assessed using RoB 2.0.

Results: Across three randomized, placebo-controlled trials (Jesse 2021, Jesse 2024, Pankaj 2018; n = 479), NK-1 receptor antagonists increased the likelihood of achieving a clinically meaningful nausea response by 44 % versus placebo (48.9 % vs 33.7 %; pooled RR 1.44, 95 % CI 0.97–2.14; p = 0.07, I² = 60 %), although this improvement narrowly missed statistical significance. Any treatment-emergent adverse events occurred in 40.9 % (99/242) of active-drug recipients versus 31.6 % (75/237) of controls, a non-significant 36 % relative increase (RR 1.36, 95 % CI 0.91–2.02; p = 0.13; I² = 57 %). Any serious side-effect rates remained low and statistically comparable (1.6 % vs 1.3 %; pooled RR 1.22, 95 % CI 0.33-4.49; p = 0.76; I² = 0 %).

Discussion: We observed a clinically meaningful 15-point absolute rise in nausea responders that narrowly missed statistical significance, without an increase in serious adverse events. This directionally favorable effect, coupled with a comparable safety profile, positions NK-1 blockade as a biologically plausible, gastric-motility-independent option for patients who fail dopamine- or serotonin-targeted agents. Heterogeneity—driven by small sample sizes and variable responder definitions—highlights the urgent need for adequately powered phase III trials using unified endpoints. Until such data mature, clinicians may consider off-label NK-1 use in carefully selected cases.


Figure: Forest Plot Showing Treatment Emergent Adverse Events, Nausea Responders and Serious Adverse Events

Disclosures:
Ashesh Das indicated no relevant financial relationships.
Palwasha Farooqi indicated no relevant financial relationships.
Venkata Dileep Kumar Veldi indicated no relevant financial relationships.
Emil Vergis Philip indicated no relevant financial relationships.
Anika Goel indicated no relevant financial relationships.
Naga Sai Akhil Reddy Gogula indicated no relevant financial relationships.
Sailesh Kumar indicated no relevant financial relationships.
Akif Khan indicated no relevant financial relationships.

Ashesh Das, MBBS¹, Palwasha Farooqi, MD², Venkata Dileep Kumar Veldi, MBBS³, Emil Vergis Philip, MBBS⁴, Anika Goel, ⁵, Naga Sai Akhil Reddy Gogula, MBBS⁶, Sailesh I S. Kumar, MBBS⁷, Akif Shahid. Khan, MBBS⁸. P6305 - NK-1 Receptor Blockade Yields a Promising Boost in Nausea Response Without Added Serious Harm in Gastroparesis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.