Trial Outcomes & Findings for Evaluate the Nephrotoxicity by 6% Hydroxyethyl Starch 130/0.4 in Old Patients During Orthopaedic Surgery (NCT NCT02361736)

NCT ID: NCT02361736

Last Updated: 2016-03-24

Results Overview

Neutrophil gelatinase-associated lipocalin (NGAL) is a small protein, which is filtered via the glomeruli and reabsorbed in the proximal tubules, and thus low concentrations of NGAL can be measured in the blood and urine.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 120 participants
• Primary outcome timeframe: -1d, 0d, 1d, 3d, 5d after surgery
• Results posted on: 2016-03-24

Participant Flow

From February 2015 to January 2016, patients were recruited and estimated for eligibility.

Exclusion criteria:Allergy and contraindication to HES; Infections and malignancies; Sepsis; History of heart failure or NYHA>Ⅲ; Renal failure or Cr>108μmol/L，BUN>8.3mmol/L;Undergoing dialytic treatments; Intracranial hemorrhages;Taking non-steroidal antiinflammatory agent for a long time

Participant milestones

Measure	Lactate Ringers Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery Lactate Ringers: Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery	Hydroxyethyl Starch 6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery Hydroxyethyl Starch: 6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery
Overall Study STARTED	60	60
Overall Study COMPLETED	59	59
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluate the Nephrotoxicity by 6% Hydroxyethyl Starch 130/0.4 in Old Patients During Orthopaedic Surgery

Baseline characteristics by cohort

Measure	Lactate Ringers n=59 Participants Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery Lactate Ringers: Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery	Hydroxyethyl Starch n=59 Participants 6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery Hydroxyethyl Starch: 6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery	Total n=118 Participants Total of all reporting groups
Age, Continuous	76.4 age STANDARD_DEVIATION 8.1 • n=5 Participants	75.9 age STANDARD_DEVIATION 7.5 • n=7 Participants	76.2 age STANDARD_DEVIATION 7.7 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	30 Participants n=7 Participants	58 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	29 Participants n=7 Participants	60 Participants n=5 Participants

PRIMARY outcome

Timeframe: -1d, 0d, 1d, 3d, 5d after surgery

Neutrophil gelatinase-associated lipocalin (NGAL) is a small protein, which is filtered via the glomeruli and reabsorbed in the proximal tubules, and thus low concentrations of NGAL can be measured in the blood and urine.

Outcome measures

Measure	Lactate Ringers n=59 Participants Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery Lactate Ringers: Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery	Hydroxyethyl Starch n=59 Participants 6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery Hydroxyethyl Starch: 6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery
Concentration of NGAL in Urine on 5 Time Point -1d	5.6 ng/ml Standard Deviation 0.7	4.9 ng/ml Standard Deviation 0.8
Concentration of NGAL in Urine on 5 Time Point 0d	5.2 ng/ml Standard Deviation 0.4	5.1 ng/ml Standard Deviation 0.3
Concentration of NGAL in Urine on 5 Time Point 1d	4.9 ng/ml Standard Deviation 0.3	4.9 ng/ml Standard Deviation 0.4
Concentration of NGAL in Urine on 5 Time Point 3d	5.0 ng/ml Standard Deviation 0.3	5.2 ng/ml Standard Deviation 0.5
Concentration of NGAL in Urine on 5 Time Point 5d	4.3 ng/ml Standard Deviation 0.8	5.1 ng/ml Standard Deviation 0.4

PRIMARY outcome

Timeframe: -1d, 0d, 1d, 3d, 5d after surgery

IL-18 is mainly created from proximal kidney tubules which is a proinflammatory factor that can be detected in earlier urine of AKI animal models.

Outcome measures

Measure	Lactate Ringers n=59 Participants Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery Lactate Ringers: Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery	Hydroxyethyl Starch n=59 Participants 6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery Hydroxyethyl Starch: 6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery
Concentration of IL-18 in Urine on 5 Time Point -1d	86.6 μg/L Standard Deviation 8.5	82.7 μg/L Standard Deviation 8.5
Concentration of IL-18 in Urine on 5 Time Point 0d	83.2 μg/L Standard Deviation 4.8	89.5 μg/L Standard Deviation 5.8
Concentration of IL-18 in Urine on 5 Time Point 1d	118.5 μg/L Standard Deviation 11.4	109.6 μg/L Standard Deviation 9.2
Concentration of IL-18 in Urine on 5 Time Point 3d	142.6 μg/L Standard Deviation 18.1	140.5 μg/L Standard Deviation 10.9
Concentration of IL-18 in Urine on 5 Time Point 5d	162.0 μg/L Standard Deviation 18.5	159.7 μg/L Standard Deviation 16.9

PRIMARY outcome

Timeframe: -1d, 0d, 1d, 3d, 5d after surgery

Outcome measures

Measure	Lactate Ringers n=59 Participants Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery Lactate Ringers: Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery	Hydroxyethyl Starch n=59 Participants 6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery Hydroxyethyl Starch: 6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery
Concentration of IL-18 in Plasma on 5 Time Point -1d	81.0 μg/L Standard Deviation 14.5	79.3 μg/L Standard Deviation 9.8
Concentration of IL-18 in Plasma on 5 Time Point 0d	81.4 μg/L Standard Deviation 9.0	81.0 μg/L Standard Deviation 10.4
Concentration of IL-18 in Plasma on 5 Time Point 1d	83.8 μg/L Standard Deviation 12.5	84.2 μg/L Standard Deviation 13.8
Concentration of IL-18 in Plasma on 5 Time Point 3d	86.5 μg/L Standard Deviation 14.1	83.4 μg/L Standard Deviation 10.2
Concentration of IL-18 in Plasma on 5 Time Point 5d	81.5 μg/L Standard Deviation 6.1	85.1 μg/L Standard Deviation 11.3

PRIMARY outcome

Timeframe: -1d, 0d, 1d, 3d, 5d after surgery

concentration of NGAL in plasma on 5 time point. Biomarkers are measured by ELISA.

Outcome measures

Measure	Lactate Ringers n=59 Participants Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery Lactate Ringers: Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery	Hydroxyethyl Starch n=59 Participants 6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery Hydroxyethyl Starch: 6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery
Concentration of NGAL in Plasma on 5 Time Point. -1d	4.1 ng/ml Standard Deviation 0.8	4.0 ng/ml Standard Deviation 0.3
Concentration of NGAL in Plasma on 5 Time Point. 0d	4.0 ng/ml Standard Deviation 0.7	4.2 ng/ml Standard Deviation 0.5
Concentration of NGAL in Plasma on 5 Time Point. 1d	4.4 ng/ml Standard Deviation 0.9	4.3 ng/ml Standard Deviation 0.5
Concentration of NGAL in Plasma on 5 Time Point. 3d	4.1 ng/ml Standard Deviation 0.7	4.2 ng/ml Standard Deviation 0.5
Concentration of NGAL in Plasma on 5 Time Point. 5d	4.3 ng/ml Standard Deviation 0.8	4.4 ng/ml Standard Deviation 0.6

SECONDARY outcome

Timeframe: -1d, 0d, 1d, 3d, 5d after surgery

Outcome measures

Measure	Lactate Ringers n=59 Participants Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery Lactate Ringers: Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery	Hydroxyethyl Starch n=59 Participants 6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery Hydroxyethyl Starch: 6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery
Concentration of β2 Microglobulin in Urine -1d	93.2 mg/L Standard Deviation 8.9	96.4 mg/L Standard Deviation 11.2
Concentration of β2 Microglobulin in Urine 0d	90.6 mg/L Standard Deviation 8.2	97.1 mg/L Standard Deviation 12.2
Concentration of β2 Microglobulin in Urine 1d	99.8 mg/L Standard Deviation 14.2	101.7 mg/L Standard Deviation 9.4
Concentration of β2 Microglobulin in Urine 3d	104.7 mg/L Standard Deviation 15.0	99.4 mg/L Standard Deviation 15.7
Concentration of β2 Microglobulin in Urine 5d	93.2 mg/L Standard Deviation 12.3	103.0 mg/L Standard Deviation 13.8

SECONDARY outcome

Timeframe: -1d, 0d, 1d, 3d, 5d after surgery

eGFR is calculated by concentration of creatinine and CKD-EPI2009

Outcome measures

Measure	Lactate Ringers n=59 Participants Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery Lactate Ringers: Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery	Hydroxyethyl Starch n=59 Participants 6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery Hydroxyethyl Starch: 6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery
Estimated Glomerular Filtration Rate(eGFR) on 5 Time Point -1d	61.9 mL/min/1.73m2 Standard Deviation 8.3	63.9 mL/min/1.73m2 Standard Deviation 14.3
Estimated Glomerular Filtration Rate(eGFR) on 5 Time Point 0d	63.5 mL/min/1.73m2 Standard Deviation 9.6	63.5 mL/min/1.73m2 Standard Deviation 13.5
Estimated Glomerular Filtration Rate(eGFR) on 5 Time Point 1d	63.0 mL/min/1.73m2 Standard Deviation 6.2	64.0 mL/min/1.73m2 Standard Deviation 14.4
Estimated Glomerular Filtration Rate(eGFR) on 5 Time Point 3d	64.0 mL/min/1.73m2 Standard Deviation 9.4	72.8 mL/min/1.73m2 Standard Deviation 10.4
Estimated Glomerular Filtration Rate(eGFR) on 5 Time Point 5d	66.4 mL/min/1.73m2 Standard Deviation 9.2	68.6 mL/min/1.73m2 Standard Deviation 12.4

SECONDARY outcome

Timeframe: -1d, 0d, 1d, 3d, 5d after surgery

ACR is calculated by the urine trace albumin divided by the urine creatinine

Outcome measures

Measure	Lactate Ringers n=59 Participants Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery Lactate Ringers: Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery	Hydroxyethyl Starch n=59 Participants 6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery Hydroxyethyl Starch: 6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery
Ratio of the Urine Trace Albumin and Creatinine(ACR) on 5 Time Point -1d	1.89 ratio Standard Deviation 0.14	1.96 ratio Standard Deviation 0.21
Ratio of the Urine Trace Albumin and Creatinine(ACR) on 5 Time Point 0d	1.84 ratio Standard Deviation 0.20	1.98 ratio Standard Deviation 0.19
Ratio of the Urine Trace Albumin and Creatinine(ACR) on 5 Time Point 1d	1.90 ratio Standard Deviation 0.19	1.90 ratio Standard Deviation 0.09
Ratio of the Urine Trace Albumin and Creatinine(ACR) on 5 Time Point 3d	1.94 ratio Standard Deviation 0.15	1.99 ratio Standard Deviation 0.13
Ratio of the Urine Trace Albumin and Creatinine(ACR) on 5 Time Point 5d	1.92 ratio Standard Deviation 0.12	1.95 ratio Standard Deviation 0.20

Adverse Events

Lactate Ringers

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Hydroxyethyl Starch

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Yuanyuan Zhang

Tianjin Medical University General Hospital

Phone: 13821685913

Email: doctorkelly@126.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place