PROGAIN Trial in Gastric Cancer Surgery (PROGAIN)

The PROGAIN Trial : A Randomized Study of Protein-enriched Parenteral Nutrition on Nitrogen Balance and Recovery in Perioperative Gastric Cancer Surgery

This randomized study will evaluate whether protein-enriched parenteral nutrition improves early postoperative recovery in patients undergoing gastrectomy for gastric cancer. Participants will be assigned to receive either protein-enriched parenteral nutrition or standard parenteral nutrition during the perioperative period. The primary outcome is nitrogen balance on postoperative day 5. Secondary outcomes include postoperative complications, recovery of oral intake, and short-term changes in nutritional status and body composition.

Study Overview

• Status: Recruiting
• Conditions: Stomach (Gastric) Cancer
• Intervention / Treatment: Drug: Protein-enriched peripheral parenteral nutrition (Winuf A+ injection); Drug: Standard peripheral parenteral nutrition (Winuf injection)

Detailed Description

Gastrectomy for gastric cancer induces a significant postoperative catabolic state, making adequate protein delivery crucial for optimal tissue healing and recovery. In the modern era of Enhanced Recovery After Surgery (ERAS) protocols, the routine use of central venous catheters for total parenteral nutrition (CPN) is heavily discouraged due to its invasiveness, infection risks, and hindrance to early mobilization. Consequently, Supplemental Parenteral Nutrition (SPN) via a peripheral route has emerged as the preferred strategy to bridge the nutritional gap when early oral intake is insufficient.

However, traditional standard peripheral parenteral nutrition (PPN) is inherently limited by osmolarity constraints to prevent peripheral phlebitis. This physical restriction often results in a critically inadequate supply of amino acids, failing to meet the heightened protein demands required to reverse acute postoperative catabolism and prevent rapid muscle depletion.

Recently, novel protein-enriched peripheral parenteral formulations have been developed to overcome this exact limitation, allowing for a higher, optimal amino acid load to be delivered safely via peripheral veins. The PROGAIN trial aims to evaluate the clinical impact of these advanced formulations. The investigators hypothesize that utilizing protein-enriched PPN, compared to standard PPN, will effectively blunt the catabolic response, significantly improve postoperative nitrogen balance, and facilitate earlier functional recovery in gastric cancer patients without compromising the principles of the ERAS pathway.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jong Hyuk Yun, MD, PhD; Phone Number: +82-10-3328-4380; Email: 109206@schmc.ac.kr
• Study Contact Backup: Name: Hyun Seob Shin; Phone Number: +82-10-7687-3350; Email: 124909@schmc.ac.kr

Study Locations

• South Korea
  • Chungcheongnam-do
    • Cheonan, Chungcheongnam-do, South Korea, 31151
      • Recruiting
      • Soonchunhyang University Cheonan Hospital
      • Contact: Jong Hyuk Yun, MD, PhD; Phone Number: +82-10-3328-4380; Email: 109206@schmc.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 19 years or older scheduled to undergo gastric cancer surgery. - Patients who have provided written informed consent to participate in this study.

Exclusion Criteria:

• Patients with uncontrolled severe systemic diseases (e.g., decompensated diabetes, cerebrovascular event within the last 6 months, sepsis, heart failure).
• Patients who have received intravenous parenteral nutrition within 7 days prior to randomization.

• Patients with severe metabolic abnormalities confirmed by preoperative laboratory tests, including but not limited to:

  • Triglyceride > 400 mg/dL
  • AST or ALT > 3 x Upper Limit of Normal (ULN)
  • Total Bilirubin > 3 x ULN
  • Serum Creatinine > 2 x ULN
  • HbA1c > 9.0%
  • Potassium < 3.0 mEq/L or > 6.0 mEq/L
  • Calcium > 12.5 mg/dL
  • Sodium > 155 mmol/L
  • Magnesium > 3.0 mg/dL
• Patients deemed inappropriate for participation in this clinical trial by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Protein-enriched PPN; Patients assigned to this arm will receive a 4th-generation, protein-enriched peripheral parenteral nutrition (PPN). The intervention will be administered for a total of 6 days, starting from preoperative day 1 (POD -1) to postoperative day 5 (POD 5), excluding the day of surgery (POD 0). The daily infusion volume is dynamically individualized; it is titrated based on the patient's target nutritional requirements and their actual daily oral intake.	Drug: Protein-enriched peripheral parenteral nutrition (Winuf A+ injection); A novel, high-amino acid peripheral parenteral nutrition formulation (Winuf A+ injection; JW Pharmaceutical) designed to provide optimal protein delivery with lower glucose load. Administered intravenously.
Active Comparator: Standard PPN; Patients assigned to this arm will receive a 3rd-generation, standard peripheral parenteral nutrition (PPN). The administration schedule is identical to the experimental arm (a total of 6 days, excluding POD 0). Similarly, the daily infusion volume is individualized and titrated according to the patient's actual oral caloric intake.	Drug: Standard peripheral parenteral nutrition (Winuf injection); A conventional, standard 3-chamber peripheral parenteral nutrition formulation (Winuf injection; JW Pharmaceutical). Administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nitrogen Balance	Change in nitrogen balance, assessed by measuring 24-hour urinary urea nitrogen excretion and calculating total daily protein intake (from both oral diet and parenteral nutrition)	Postoperative Day 5 (POD 5)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal Muscle Index (Sarcopenia Assessment)	Quantitative changes in skeletal muscle mass evaluated using the Skeletal Muscle Index (SMI). SMI is a continuous physiological measurement derived from cross-sectional imaging (such as abdominal computed tomography) and/or bioelectrical impedance analysis (BIA). Because it is a continuous physiological variable, there are no predefined minimum or maximum values on a scale. Higher SMI values indicate greater skeletal muscle mass, representing a better clinical outcome (prevention of muscle depletion).	Baseline (preoperative), and 6 months postoperativel
Nutritional Status Assessed by GLIM Criteria	Change in nutritional status evaluated using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Participants will be categorized into normal nutritional status, moderate malnutrition, or severe malnutrition. This is a categorical assessment, not a numerical scale with minimum or maximum values. The "normal nutritional status" category represents the best clinical outcome, while "severe malnutrition" represents the worst.	Baseline, 1 month, 3 months, and 6 months postoperatively
Complications	Rate of postoperative complications classified as Clavien-Dindo grade 2 or higher, specifically monitoring for delayed gastric emptying (DGE) and infectious complications (surgical site infection, pneumonia). The Clavien-Dindo classification is an ordinal scale used to grade surgical complications. The scale ranges from Grade I (minimum value, mild complication) to Grade V (maximum value, death of a patient). A higher grade indicates a more severe complication, representing a worse clinical outcome.	Up to 30 days postoperatively
Glycemic Control	Frequency of hyperglycemic events, defined as plasma glucose levels of 180 mg/dL or higher, during the parenteral nutrition administration period.	Postoperative Day 1 to Day 5
Functional Recovery	Recovery of Oral Intake, Length of Hospital Stay	Up to hospital discharge (expected average up to 7-10 days)
Prognostic Nutritional Index (PNI)	Change in the Prognostic Nutritional Index (PNI), calculated based on serum albumin concentration and total peripheral lymphocyte count. Because it is a continuous physiological calculated index, there are no predefined minimum or maximum values on a scale. Higher PNI values indicate better nutritional and immunological status, representing a better clinical outcome.	Baseline, 1 month, 3 months, and 6 months postoperatively
C-Reactive Protein to Albumin Ratio (CAR)	Change in the C-Reactive Protein to Albumin Ratio (CAR), calculated by dividing the serum C-reactive protein (CRP) level by the serum albumin level. This is a continuous physiological ratio, thus there are no predefined minimum or maximum values. Lower CAR values indicate lower systemic inflammation and better nutritional status, representing a better clinical outcome.	Baseline, 1 month, 3 months, and 6 months postoperatively
Modified Glasgow Prognostic Score (mGPS)	Change in the modified Glasgow Prognostic Score (mGPS), an inflammation-based prognostic score based on serum CRP and albumin thresholds. The mGPS is an ordinal scale with predefined values of 0, 1, or 2 (minimum value: 0, maximum value: 2). A lower score indicates a lower level of systemic inflammation, representing a better clinical outcome (0 is the best outcome, 2 is the worst outcome).	Baseline, 1 month, 3 months, and 6 months postoperatively

Collaborators and Investigators

• Sponsor: Soonchunhyang University Hospital
• Collaborators: JW Pharmaceutical
• Investigators: Principal Investigator: Geum Jong Song, MD, PhD, Soonchunhyang University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: March 14, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 16, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Enhanced Recovery After Surgery; Stomach Neoplasms; Gastrectomy; Parenteral Nutrition; Nitrogen Balance; Perioperative nutrition; Protein enriched
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Signs and Symptoms, Digestive; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Stomach Neoplasms; Hyperphagia
• Other Study ID Numbers: 2025-11-024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data that underlie the results reported in this article will be shared upon reasonable request to the corresponding author.
• IPD Sharing Time Frame: Beginning 6 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Data will be shared with researchers who provide a methodologically sound proposal, subject to approval by the Institutional Review Board (IRB) and a formal data use agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No