Clinical trial NCT02663960: Compare Efficacy and Simplicity of Regional Citrate Anticoagulation With Fixed Dose Versus Adjusted Citrate Program
Official title: Is Regional Citrate Anticoagulation With Fixed Citrate Blood Concentration More Effective and Easy-to-handle Than Adjusted-dose Protocol in Adult Critically Ill Patients? A Cohort Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Critical Illness
Kidney Replacement Disorder
Coagulation; Intravascular
Keywords: Regional citrate anticoagulation
Protocol
Filter lifespan
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2016-01-26
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Anticoagulation is required to prevent clotting in the extracorporeal circuit during continuous renal replacement therapy (CRRT). Regional citrate anticoagulation has many advantages regarding bleeding risk and filter survival. However, in clinical practice, its use worldwide has been limited by cumbersome protocols . In order to establish a simple scheme for universal application. In Aug 2015, the investigators have adopted a new protocol using a fixed citrate concentration in the filter of about 4 mmol/L (called fixed group for short) instead of conventional adjusted citrate doses according to postfilter ionized calcium levels of less than 0.4mmol/l (adjusted group), and speculated the abilities on efficacy and safety as well as convenience.

Detailed description: Design: This study was conducted as a single-centre, cohort study. All patients older than 18 years of age who required veno-venous hemofiltration (CVVH) were consecutively screened forward (prospective) or backward (retrospective) from August, 2015 and until the expected sample size was reached.

Study protocol: Before and after implementation of a new protocol, apart from the flow rate of any supplementation (Anticoagulant-citrate-dextrose solution, 5% sodium bicarbonate injection and 10% calcium gluconate injection), CVVH was performed using same standards, including devices (Aquarius or Diapact® CRRT), venous catheter (a double lumen 12-F catheter, Arrow International Inc., USA), haemofilter (DIACAP Acute L, 2.0 m2, B. Braun Melsungen AG, Germany), commercial replacement fluids (Na+113, Cl-118, Mg++0.797, Ca++1.60, glucose 10.6mmo/l and zero bicarbonate; Qing-shan-li-kang pharmaceutical Co.,Ltd. Cheng-du, China) and Anticoagulant-citrate-dextrose solution-A (ACD-A) (Na+ 224, citrate 113, bicarbonate 203mmol/l, Fresenius Kabi, Italy) as well as monitoring algorithm. The first sample of postfilter and systemic ionized calcium was done two hours after initiation of CVVH and every six to eight hours during the first 24 hours. Afterwards, these measurements were done according to clinical needs for maintaining normal ionized calcium levels and blood pH value.

The group of fixed citrate concentration: ACD-A was administered in the prefilter ahead of the blood pump and the infusion rate was fixed and set to meet a circuit citrate concentration of 4 mmol/l. Calcium Gluconate 10% Injection was infused through the return line of the circuit and the substitution flow was initiated with 0.8 mmol calcium per liter total effluent flow and then be adjusted to obtain systemic ionized calcium levels between 0.90 and 1.2 mmol/l. Sodium bicarbonate 5% injection was infused through the return line of the circuit and the substitution flow was initiated with 3.3% of replacement fluid flow and then be adjusted to obtain blood pH value in the normal range (7.35 to 7.45)

The group of adjusted citrate doses:ACD-A was administered in the prefilter ahead of the blood pump and the starting infusion rate was 2.5 % of blood flow and then be adjusted to obtain postfilter ionized calcium levels of less than 0.40 mmol/l. Calcium Gluconate 10% Injection was infused through the return line of the circuit and the substitution flow was initiated with 7.3% of ACD-A flow, and then be adjusted to obtain systemic ionized calcium levels between 0.90 and 1.2 mmol/l. Sodium bicarbonate 5% injection was infused through the return line of the circuit and the starting infusion rate was 4% of replacement fluid flow,and then be adjusted to obtain blood pH value in the normal range (7.35 to 7.45)

Statistical analyses: groups were compared by using Fisher's exact test, Student's t test or Mann-Whitney rank-sum test as appropriate. Circuit lifetime was evaluated with Kaplan-Meier survival analysis and survival curves distribution was compared with the Log Rank test. Univariate and multivariate analysis were used to identify factors associated with mean filter lifetime in all group patients.

Eligibility criteria: Inclusion Criteria:

* All patients older than 18 years of age who required CVVH were consecutively screened

Exclusion Criteria:

* Requiring extracorporeal membrane oxygenation (ECMO) at the time of hemofiltration, insufficient data available or missing and running time less than 6 hours

Primary outcomes:
measure: the survival time of the first filter due to unexpected disconnection
timeFrame: the time period on CVVH, maximum 72 hour
Secondary outcomes:
measure: the overall survival time of the first filter
timeFrame: the time period on CVVH, maximum 72 hour
measure: the frequency of change in the infusion pump rate of calcium gluconate 10% Injection
timeFrame: the time period on CVVH, maximum 72 hour
measure: the frequency of change in the infusion pump rate of Sodium Bicarbonate 5% Injection
timeFrame: the time period on CVVH, maximum 72 hour
measure: the frequency of change in the infusion pump rate of Anticoagulant Citrate Dextrose Solution
timeFrame: the time period on CVVH, maximum 72 hour
measure: incidences of severe metabolic disorders
timeFrame: the time period on CVVH, maximum 72 hour
Other outcomes:
Locations:
city: Beijing
country: China
facility: MICU of Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Department of medical ICU,Peking Union Medical College Hospital
name: Bin Du, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shi Y, Qin HY, Peng JM, Hu XY, Du B. Feasibility and efficacy of modified fixed citrate concentration protocol using only commercial preparations in critically ill patients: a prospective cohort study with a historical control group. BMC Anesthesiol. 2021 Mar 30;21(1):96. doi: 10.1186/s12871-021-01319-4.