Enteral Supplementation With Sodium Dihydrogen Phosphate and Disodium Hydrogen Phosphate Granules for the Treatment of Hypophosphatemia.

Official title

A Prospective Clinical Study Evaluating the Effectiveness and Safety of Enteral Supplementation With Sodium Dihydrogen Phosphate and Disodium Hydrogen Phosphate Granules for Varying Degrees of Hypophosphatemia

Overview

The purpose of this clinical trial is to evaluate the efficacy and safety of Sodium Dihydrogen Phosphate and Disodium Hydrogen Phosphate Granules for the treatment of participants with mild, moderate, and severe hypophosphatemia. The main questions it aims to answer are: Does enteral supplementation of Sodium Dihydrogen Phosphate and Disodium Hydrogen Phosphate Granules elevate participants' serum phosphorus? Does enteral supplementation of Sodium Dihydrogen Phosphate and Disodium Hydrogen Phosphate Granules cause gastrointestinal complications? Participants with hypophosphatemia will receive Sodium Dihydrogen Phosphate and Disodium Hydrogen Phosphate Granules orally or via nasogastric tube to observe the efficacy and safety of enteral phosphate supplementation. Participants will take Sodium Dihydrogen Phosphate and Disodium Hydrogen Phosphate Granules daily, with varying doses based on the severity of hypophosphatemia, for a maximum of 14 days. The effect of phosphate supplementation will be assessed daily through blood draws, and their gastrointestinal symptoms will be recorded.

Interventions

• Drug Sodium Dihydrogen Phosphate and Disodium Hydrogen Phosphate Granules
  After signing the informed consent form (ICF), eligible subjects were stratified based on the severity of hypophosphatemia during the screening period: mild hypophosphatemia (0.65-0.80 mmol/L), moderate hypophosphatemia (0.32-0.64 mmol/L), or severe hypophosphatemia (\<0.32 mmol/L). Following enrollment, subjects entered a treatment period of up to 14 days. All subjects received a differentiated phosphate supplementation strategy based on actual body weight: subjects with mild hypophosphatemia

Primary outcome measures

• The rate of achieving target serum phosphorus levels (≥0.80 mmol/L) with enteral phosphorus supplementation in patients during the study period. [Time frame: Within 14 days of study enrollment]

Secondary outcome measures (6)

• The magnitude of serum phosphorus elevation per 1 mmol of enteral phosphorus supplementation in patients during the study period. [Time frame: The total duration from the start of enteral phosphorus supplementation to the end of phosphorus therapy is less than 14 days.]
• Average time to achieve target serum phosphorus concentration during phosphorus replacement therapy [Time frame: The total duration from the initiation of enteral phosphate supplementation to the normalization of serum phosphate levels is less than 14 days.]
• The proportion of patients with a blood phosphorus concentration increase of less than 0.1 mmol/L over any 72-hour period during phosphorus supplementation therapy. [Time frame: From the initiation of enteral phosphate supplementation to the end of treatment, the increase in serum phosphate levels within any 72-hour period occurs over a total duration of less than 14 days.]
• Proportion of withdrawals due to intolerance to enteral phosphorus supplementation [Time frame: During the study period, the maximum duration shall not exceed 14 days.]
• Incidence of Adverse Reactions [Time frame: The entire duration of the study, from initiation to completion, shall not exceed 14 days.]
• Changes in APACHE II and SOFA scores from baseline [Time frame: APACHE II and SOFA scores within 24 hours before the start of the study and within 24 hours before the end of the study]

Eligibility criteria

Inclusion criteria

• Aged 18-80 years (inclusive), regardless of gender;
• ICU inpatients with a serum phosphate concentration <0.80 mmol/L, and for whom the clinician determines phosphate supplementation is required;
• Ability to receive enteral nutrition, with a daily enteral caloric intake ≥10 kcal/kg/day;
• The subject or their legal guardian fully understands the purpose and significance of this trial, voluntarily agrees to participate, provides written informed consent, and is willing to strictly adhere to the clinical study protocol and complete the study.

Exclusion criteria

• Pregnant and lactating women;
• Patients with contraindications for enteral administration, such as acute upper gastrointestinal bleeding, mechanical intestinal obstruction, severe acute pancreatitis, digestive tract fistula, gastrointestinal dysfunction, intra-abdominal hypertension, enteral feeding intolerance, or continuous gastrointestinal decompression;
• Expected ICU stay ≤96 hours;
• Known allergy to any component of the investigational drug or drugs with a similar chemical structure;
• Severe renal impairment: estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m²;
• Subjects with hyperthyroidism requiring clinical intervention;
• Subjects requiring sodium restriction;
• Other conditions deemed by the investigator as unsuitable for inclusion.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan

Publications

• Cheng YC, Beh JY, Wu PH, Tsai NY, Jao SW. Early botulinum toxin injection reduces pain after hemorrhoidectomy: a pilot study. Tech Coloproctol. 2022 Jan;26(1):53-60. doi: 10.1007/s10151-021-02542-4. Epub 2021 Oct 27. PMID 34705137
• Kaya U, Dal Yilmaz U. Ideal Suggestions for Discharge Training and Telephone Counseling of Patients With Coronary Artery Bypass Graft Surgery: A Randomized Controlled and Experimental Study. J Korean Med Sci. 2022 Sep 5;37(35):e269. doi: 10.3346/jkms.2022.37.e269. PMID 36065653
• Felsenfeld AJ, Levine BS. Approach to treatment of hypophosphatemia. Am J Kidney Dis. 2012 Oct;60(4):655-61. doi: 10.1053/j.ajkd.2012.03.024. Epub 2012 Aug 3. PMID 22863286
• Geerse DA, Bindels AJ, Kuiper MA, Roos AN, Spronk PE, Schultz MJ. Treatment of hypophosphatemia in the intensive care unit: a review. Crit Care. 2010;14(4):R147. doi: 10.1186/cc9215. Epub 2010 Aug 3. PMID 20682049
• Nguyen CD, Panganiban HP, Fazio T, Karahalios A, Ankravs MJ, MacIsaac CM, Rechnitzer T, Arno L, Tran-Duy A, McAlister S, Ali Abdelhamid Y, Deane AM. A Randomized Noninferiority Trial to Compare Enteral to Parenteral Phosphate Replacement on Biochemistry, Waste, and Environmental Impact and Healthcare Cost in Critically Ill Patients With Mild to Moderate Hypophosphatemia. Crit Care Med. 2024 Jul 1; PMID 38537225
• Engwerda E, van den Berg M, Blans M, Bech A, de Boer H. Efficacy and safety of a phosphate replacement strategy for severe hypophosphatemia in the ICU. Neth J Med. 2018 Dec;76(10):437-441. PMID 30569887
• Lair CS, Brown LS, Edwards A, Jacob T, Brion LP, Jaleel M. Quality improvement project in a neonatal intensive care unit reduced the prevalence and duration of hypophosphatemia with significant and sustainable results. Nutr Clin Pract. 2023 Dec;38(6):1379-1391. doi: 10.1002/ncp.10986. Epub 2023 Apr 12. PMID 37042685
• Rubio-Aliaga I, Krapf R. Phosphate intake, hyperphosphatemia, and kidney function. Pflugers Arch. 2022 Aug;474(8):935-947. doi: 10.1007/s00424-022-02691-x. Epub 2022 May 5. PMID 35511366

Identifiers

NCT: NCT07233889 · ICU202501

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗