Acute Kidney Injury, Critically Ill Patients Requiring Continuous Renal Replacement Therapy, Sepsis
Conditions
Keywords
CRRT, Phosphate-containing replacement fluid
Brief summary
Brief Summary: Evaluating a New Phosphate-Containing Fluid for Blood Purification (CRRT) Why is this study being done? Patients in the Intensive Care Unit (ICU) often need a treatment called Continuous Renal Replacement Therapy (CRRT). This is a type of blood purification that acts like an artificial kidney to clear toxins and extra fluid from the body. A common problem during this treatment is that vital minerals, like phosphate, are washed out of the blood along with the toxins. Low phosphate can lead to muscle weakness and breathing problems. Currently, doctors must manually add phosphate to the treatment fluids, which can be inconsistent. This study aims to test a new, pre-mixed fluid that already contains phosphate to see if it works better and is safe. What are the main questions the study aims to answer? Does the new fluid help keep phosphate at a healthy level in the blood during the first 72 hours of treatment? How does the new fluid affect kidney function compared to the standard fluid? Is the new fluid safe for patients to use? Who can take part in this study? The study is looking for adults (18 and older) who: Are in the ICU and need CRRT treatment as decided by their doctor. Are expected to need this treatment for at least 72 hours. Are willing to participate (or have a legal guardian who agrees). People who are pregnant, have known allergies to the fluid ingredients, or have very low blood pressure that cannot be corrected may not be able to join. How will the research happen? This is a "double-blind" study involving 220 participants across 15 hospitals. This means neither the patients nor the doctors will know which fluid is being used until the study is over. Participants will be put into one of two groups by a computer: Group 1 (New Fluid): Receives the blood purification fluid that has phosphate already in it. Group 2 (Standard Fluid): Receives the standard fluid that does not have phosphate. What will participants have to do? Receive Treatment: Participants will receive their assigned fluid during their normal CRRT care for up to 7 days. Blood Tests: Doctors will take regular blood samples to check mineral levels and kidney health. Monitoring: The medical team will closely watch participants for any side effects or safety concerns. Follow-up: There will be a safety check-up 7 days after the treatment ends. Possible Benefits and Risks The new fluid may help prevent low phosphate levels, which could help with recovery. However, as with any medical treatment, there is a risk of side effects or electrolyte imbalances. The research team will monitor every participant 24/7 to ensure their safety.
Detailed description
Scientific Rationale and Study Objective: Continuous renal replacement therapy (CRRT) is a standard life-support intervention in the ICU. However, standard phosphate-free replacement fluids frequently lead to unintended phosphorus removal, causing treatment-induced hypophosphatemia. This electrolyte imbalance is clinically significant, as it is linked to impaired muscle function and delayed respiratory weaning. This Phase III trial evaluates a novel, pre-mixed, phosphate-containing replacement fluid designed to maintain physiological phosphorus homeostasis and provide high-quality evidence for its standardized use in preventing CRRT-induced complications. Study Design and Multicenter Implementation: This is a randomized, double-blind, parallel-controlled trial conducted across 15 tertiary medical centers in China. A total of 220 participants requiring ≥ 72 hours of CRRT will be randomized 1:1 via a central Interactive Web Response System (IWRS). The study utilizes a dual-primary endpoint framework to demonstrate that the phosphate-containing fluid is non-inferior to standard therapy in renal replacement efficacy (creatinine clearance) and superior in preventing hypophosphatemia (serum phosphorus \< 0.81 mmol/L). All sites follow a standardized CRRT protocol, including unified blood flow rates and effluent dosing, to minimize confounding variables. Blinding and Intervention Protocol: To ensure the integrity of the double-blind design, the experimental phosphate-containing fluid and the control fluid are identical in appearance, labeling, and packaging. The intervention lasts for a maximum of 7 days, followed by a 7-day post-treatment follow-up. Clinical monitoring includes regular assessments of vital signs, fluid balance, and blood gas analysis. Secondary outcomes focus on organ function (SOFA scores), mechanical ventilation duration, and comprehensive metabolic stability, including glycemic and electrolyte balance. Data Management and Quality Assurance: Data integrity is managed through an Electronic Data Capture (EDC) system with rigorous Source Data Verification (SDV) at all 15 sites to ensure compliance with Good Clinical Practice (GCP). An independent Data Monitoring Committee (DMC) is established to periodically review safety data and protect participant welfare, ensuring the scientific rigor and safety of this multicenter clinical investigation.
Interventions
DRUGPhosphate-containing Replacement Fluid
Phosphate-containing Replacement Fluid is an investigational Class 2.3 modified chemical drug approved by the NMPA (No. 2021LP00824). It is a premixed, electrolyte-balanced replacement fluid containing phosphorus. The solution is administered via the extracorporeal circuit during Continuous Renal Replacement Therapy (CRRT). The dosage and flow rate are standardized according to the subject's body weight and clinical requirements (typically 25-35 mL/kg/h).
DRUGStandard Phosphate-free Replacement Fluid
A marketed phosphate-free replacement fluid (standard of care). Administration via extracorporeal circuit with doses identical to the experimental group. Treatment is expected for 72 hours, up to a maximum of 7 days, or until CRRT is clinically terminated. This comparator evaluates the efficacy of the phosphate-containing solution in preventing treatment-induced hypophosphatemia.
Sponsors
Sun Yat-sen University
Chengdu Qingshan Likang Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Blinding Implementation: This is a double-blind study. Experimental phosphate-containing fluid and standard control fluid are provided in identical 4,000 mL bags with masked labeling to ensure indistinguishable appearance (color, clarity, volume). Randomization & Independence: Randomization and packaging are managed by an independent unblinded statistician not involved in trial conduct. All parties, including the sponsor, investigators, participants, and outcome assessors, remain blinded to treatment allocation until the official database lock and the Blinded Data Review Meeting (DRM). Unblinding Protocol: A single-stage unblinding occurs only after the database is locked. No interim efficacy analysis is planned. Emergency unblinding via IWRS is permitted only if treatment knowledge is critical for participant safety (e.g., SAEs). Unblinded participants will be withdrawn and documented as dropouts. All emergency unblinding events must be reported to the sponsor within 24 hours.
Intervention model description
This is a multicenter, randomized, double-blind, parallel-controlled, Phase III study. A total of 220 eligible participants will be randomized in a 1:1 ratio to either the experimental group (phosphate-containing replacement fluid) or the control group (standard phosphate-free fluid). Stratified Randomization: Randomization is managed via a central Interactive Web Response System (IWRS), stratified by: Baseline Serum Phosphorus: (\< 0.81 mmol/L; 0.81-1.45 mmol/L; \> 1.45 mmol/L). Baseline Serum Creatinine: (≥ 353 μmol/L; \< 353 μmol/L). Blinding Integrity: To maintain the double-blind design, the experimental and control fluids are provided in identical 4,000 mL bags with masked labeling. Participants, investigators, and outcome assessors remain blinded throughout the intervention period.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must meet all of the following criteria to be eligible for the study: 1. Aged 18 years or older, regardless of gender. 2. Meet the clinical indications for Continuous Renal Replacement Therapy (CRRT) as defined by the "Standard Operating Procedures for Blood Purification (2021 Edition)" and assessed by a qualified nephrologist or intensive care physician. 3. Expected continuous blood purification duration is 72 hours or longer. 4. The participant or their legal guardian has a full understanding of the purpose and significance of the trial, voluntarily agrees to participate and comply with the study procedures, and has signed the written Informed Consent Form (ICF).
Exclusion criteria
* Participants meeting any of the following criteria will be excluded from the study: 1. Known allergy to any component of the investigational drug, or individuals with an allergic constitution. 2. Inability to establish suitable vascular access for CRRT. 3. Persistent hypotension (Systolic Blood Pressure \< 90 mmHg or Mean Arterial Pressure \< 65 mmHg) that is difficult to correct, unless judged by the investigator as potentially correctable with intervention. 4. Presence of malignant tumors with systemic metastasis (except for those who previously underwent radical surgery without recurrence). 5. Pregnant or breastfeeding women. 6. Receipt of any form of renal replacement therapy (RRT) or blood purification treatment within 24 hours prior to screening. 7. Receipt of peritoneal dialysis within 24 hours prior to screening. 8. Participation in any other clinical trial involving investigational drugs or devices within 1 month prior to screening. 9. Any other condition or reason that, in the opinion of the investigator, makes the patient unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Creatinine at 72 Hours | 72 hours | Percentage change in serum creatinine from baseline to 72 hours to evaluate the non-inferiority of the phosphate-containing fluid in solute clearance. |
| Incidence of Hypophosphatemia Within 72 Hours | Up to 72 hours | Percentage of participants with any measured serum phosphorus \< 0.81 mmol/L during the 72-hour treatment window. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Serum Creatinine | Baseline, 24 hours, 48 hours, and 72 hours after CRRT initiation, and every 12-24 hours thereafter until the end of treatment (up to 7 days). | The relative change in serum creatinine concentration compared to the baseline value. It is calculated as: \[(Value at post-treatment visit - Baseline Value) / Baseline Value\] x 100%. |
| Sequential Organ Failure Assessment (SOFA) Score | Baseline, 24 hours, 48 hours, and 72 hours after CRRT initiation, and every 24 hours thereafter until the end of treatment (up to 7 days). | The Sequential Organ Failure Assessment (SOFA) score is used to track a person's status during the stay in an intensive care unit (ICU) to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. The total score ranges from 0 to 24, with higher scores indicating more severe organ dysfunction. |
| Total Amount of Exogenous Phosphorus Supplementation | Within 24 hours, 48 hours, 72 hours, and during the entire treatment period (up to 7 days) after CRRT initiation. | The cumulative amount of exogenous phosphorus administered to participants to maintain serum phosphate levels within the target range. |
| Incidence of Exogenous Phosphorus Supplementation | Within 24 hours, 48 hours, 72 hours, and during the entire treatment period (up to 7 days) after CRRT initiation. | The percentage of participants who required exogenous phosphorus supplementation during the CRRT procedure to maintain serum phosphorus levels within the target range. This measure evaluates the clinical demand for phosphorus replacement in both groups. |
| Change From Baseline in Serum Phosphorus Levels | Baseline, 24 hours, 48 hours, and 72 hours after CRRT initiation, and every 24 hours thereafter until the end of treatment (up to 7 days). | The absolute change in serum phosphorus concentrations measured at each specified time point relative to the baseline value. This measure evaluates the stability of phosphate homeostasis during the CRRT procedure. |
| Duration of Mechanical Ventilation During the Treatment Period | From the initiation of CRRT through 7 days after the completion of CRRT treatment. | The cumulative number of hours the participant requires mechanical ventilation (including invasive and non-invasive). The measurement period starts from the initiation of CRRT and continues until 7 days after the cessation of CRRT treatment. |
| Incidence of Hypophosphatemia (Excluding the 72-hour Primary Endpoint) | Within 24 hours, 48 hours, and during the entire treatment period (up to 7 days) after CRRT initiation. | The percentage of participants who develop hypophosphatemia, defined as serum phosphorus levels below 0.81 mmol/L. This measure specifically tracks the occurrence within the first 24 hours, 48 hours, and throughout the entire treatment course to assess the early and overall safety profile, distinct from the primary endpoint assessed at 72 hours. |
| Duration of Hypophosphatemia | Within the first 24 hours, 48 hours, 72 hours, and during the entire treatment period (up to 7 days) after CRRT initiation. | The cumulative duration (in hours) during which the participant's serum phosphorus level is below 0.81 mmol/L. The duration is calculated based on serial measurements: every 6 hours during the first 72 hours, and every 12 hours thereafter until the end of the treatment period. |
| Incidence of Hyperphosphatemia | Within the first 24 hours, 48 hours, 72 hours, and during the entire treatment period (up to 7 days) after CRRT initiation. | The percentage of participants who develop hyperphosphatemia, defined as a serum phosphorus level above 1.45 mmol/L (or according to the institutional standard), at any time during the specified intervals. |
| Duration of Hyperphosphatemia | Within 24 hours, 48 hours, 72 hours, and during the entire treatment period (up to 7 days) after CRRT initiation. | The cumulative duration (in hours) during which the participant's serum phosphorus level is above 1.45 mmol/L. The duration is calculated based on serial measurements: every 6 hours during the first 72 hours, and every 12 hours thereafter until the end of the treatment period. |
| Recovery Rate of Hyperphosphatemia | 24 to 48 hours, 48 to 72 hours, and from 72 hours until the end of the treatment period (if treatment exceeds 72 hours). | The percentage of participants with baseline hyperphosphatemia (serum phosphorus \> 1.45 mmol/L) who achieve and maintain normal serum phosphorus levels (≤ 1.45 mmol/L) during specified intervals. Recovery is defined as phosphorus levels remaining ≤ 1.45 mmol/L consistently from 24 to 48 hours, 48 to 72 hours, and from 72 hours until the end of the treatment period (if treatment exceeds 72 hours). |
| Proportion of Participants With Normal Serum Phosphorus Levels | At 48 hours, 72 hours after CRRT initiation, and every 24 hours thereafter until the end of treatment (up to 7 days). | The percentage of participants whose serum phosphorus levels are within the normal range, defined as ≤ 1.45 mmol/L and ≥ 0.81 mmol/L. This measure is assessed once daily through laboratory monitoring. |
| Incidence of Hyperglycemia | Within 48 hours, 72 hours, and during the entire treatment period (up to 7 days) after CRRT initiation. | The percentage of participants with baseline blood glucose \< 10 mmol/L who develop hyperglycemia (defined as blood glucose ≥ 10 mmol/L) at any point during the specified time intervals. This measure evaluates the impact of the intervention on glycemic control. |
| Incidence of Hypoglycemia | Within 48 hours, 72 hours, and during the entire treatment period (up to 7 days) after CRRT initiation. | The percentage of participants with baseline blood glucose ≥ 3.9 mmol/L who develop hypoglycemia (defined as blood glucose \< 3.9 mmol/L) at any point during the specified time intervals. This measure is used to evaluate the metabolic safety of the intervention. |
| Incidence of Electrolyte and Acid-Base Deviations | Baseline, 24 hours, 48 hours, 72 hours after CRRT initiation, and every 24 hours thereafter until the end of treatment (up to 7 days). | The percentage of participants with electrolyte and acid-base values outside the clinical reference ranges for Sodium (Na+), Calcium (Ca2+), Magnesium (Mg2+), Chloride (Cl-), Bicarbonate (HCO3-), and pH. Deviations will be analyzed and reported separately as the proportion of participants with values below the lower limit of normal (LLN) and the proportion with values above the upper limit of normal (ULN) at each specified time point. |
| Incidence of Adverse Events | From the initiation of CRRT through 7 days after the completion of CRRT treatment. | Percentage of participants experiencing at least one adverse event (AE). An AE is defined as any untoward medical occurrence, including worsening of pre-existing conditions, new clinical symptoms, signs, or clinically significant laboratory abnormalities, regardless of causal relationship with the study drug. Note: Expected disease progression related to CRRT indications or comorbidities is not considered an AE unless it results in death or is more severe than expected. Notably, hypophosphatemia and hyperphosphatemia are reported separately and are NOT counted as AEs in this study. |
| Incidence of Clinically Significant Abnormalities During the Treatment Period | From the initiation of CRRT until the end of CRRT treatment (up to 7 days). | The percentage of participants experiencing at least one clinically significant abnormal change in vital signs, 12-lead electrocardiograms (ECG), or laboratory parameters. "During the treatment period" is defined as the interval from the initiation of Continuous Renal Replacement Therapy (CRRT) until the cessation of the treatment. |
Countries
China
Contacts
CONTACTJianfeng Wu, MD PhD
CONTACTChuanxi Chen, MD PhD
Outcome results
None listed