Clinical trial NCT05911438: Accelerated Recovery for Total Knee Replacement Surgery With Preoperative Intravenous Iron Combined With Human Erythropoietin for Rapid Hematopoietic Mobilization to Prevent Postoperative Anemia
Official title: Accelerated Recovery for Total Knee Replacement Surgery With Preoperative Intravenous Iron Combined With Human Erythropoietin for Rapid Hematopoietic Mobilization to Prevent Postoperative Anemia: a Multicenter Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Total Knee Arthroplasty
Keywords: Human Erythropoietin
Ferric Derisomaltose Injection
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2023-06-22
Enrollment: 419
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized, placebo-controlled, multicenter research design to investigate the effectiveness and safety of a single-dose intravenous iron combined with HuEPO hematopoietic mobilization before surgery in patients undergoing unilateral total knee arthroplasty for the first time.

Detailed description: This study is a randomized, placebo-controlled, multicenter research design to investigate the effectiveness and safety of a single-dose intravenous iron combined with HuEPO hematopoietic mobilization before surgery in patients undergoing unilateral total knee arthroplasty for the first time.

The study consists of a pilot trial and a formal trial. The pilot trial plans to enroll 20 subjects, with 10 subjects randomly assigned to the experimental group and 10 subjects to the control group. After the successful completion of the pilot trial, its safety and effectiveness, as determined by the investigators, hematologists, orthopedic surgeons, and statisticians, and the formal trial will be initiated. The relevant information and results will also be submitted to the ethics review committee. The formal trial plans to enroll 399 eligible subjects, with a random allocation ratio of 2:1 to the experimental group or the control group.

To ensure the safety of the subjects, the last subject in the pilot trial will be followed up for 21 days after surgery. The safety and effectiveness of the pilot trial results will be discussed by the investigators, hematologists, orthopedic surgeons, and statisticians before initiating the formal trial. The timing of medication, sample size, and visit points in the formal trial may be adjusted appropriately based on the results of the pilot trial.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 75 years (inclusive) and no gender restriction at the time of signing the informed consent form (ICF).
* Patients who meet the diagnostic criteria for osteoarthritis according to the American College of Rheumatology (ACR) and are undergoing primary total knee arthroplasty due to end-stage osteoarthritis. Flexion deformity \<30°, varus deformity \<30°, valgus deformity \<20°.
* Baseline hemoglobin level: 100g/L \< Hb \< 130g/L.
* No deep venous thrombosis observed on preoperative bilateral lower limb venous color Doppler ultrasound.
* The subject understands and voluntarily signs the written informed consent form (ICF) and is capable of complying with the scheduled visits and related procedures as outlined in the protocol.

Exclusion Criteria:

* Known allergy to any excipients in the investigational drugs iron sucrose and erythropoietin or a history of multiple allergies.
* Mean corpuscular volume (MCV) \> 100 fL.
* Numeric Rating Scale (NRS) score ≥ 3.
* Presence of iron overload (serum ferritin \> 800 ng/ml) or iron utilization disorders (such as hemochromatosis and iron deposition disorders).
* Blood disorders other than iron-deficiency anemia.
* Blood transfusion within the past 30 days.
* Use of iron preparations or HuEPO for the treatment of anemia within the past 30 days.
* History of deep vein thrombosis or pulmonary embolism.
* Patients with hypophosphatemia due to various causes.
* BMI \< 18.5 kg/m2 or body weight \< 50 kg.
* History of recent myocardial infarction, angina pectoris, cerebral infarction, or epileptic seizures within the past 6 months.
* Use of medications affecting coagulation and antiplatelet function within the past week.
* Moderate liver impairment: Decompensated liver cirrhosis or hepatitis, ALT, AST \> 3 times the upper limit of normal (ULN).
* Moderate renal impairment: Serum creatinine (Cr) \> 150 µmol/L.
* HIV or syphilis patients.
* Pregnant or lactating women.
* Participants who have previously participated in other clinical trials, provided the previous investigational drug exposure did not exceed 5 half-lives.
* Acute infection, rheumatoid arthritis, or significant joint inflammation.
* Patients deemed unsuitable to participate in this clinical trial by the investigator.

Primary outcomes:
measure: Hemoglobin concentration
timeFrame: postoperative 14±3 days
Secondary outcomes:
measure: Total blood loss
timeFrame: postoperative 3±1 days
measure: Transfusion rate and amount
timeFrame: postoperative 14±3 days
measure: Assess changes in serum ferritin and transferrin saturation
timeFrame: postoperative 14±3 days and 28±5 days
measure: Quality of life indicators (SF-12)
timeFrame: postoperative 28±5 days and 90±12 days
measure: The rates of adverse events (AE)
timeFrame: postoperative 90±12 days
measure: The rates of serious adverse events (SAE)
timeFrame: postoperative 90±12 days
measure: The rates of laboratory abnormalities
timeFrame: postoperative 90±12 days
measure: The rates of adverse events leading to drug discontinuation
timeFrame: postoperative 90±12 days
measure: The rates of adverse events leading to permanent discontinuation
timeFrame: postoperative 90±12 days
measure: The rates of adverse events leading to early withdrawal from the study
timeFrame: postoperative 90±12 days
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
References: