Critical IllnessPhase 4NCT02663960
Compare Efficacy and Simplicity of Regional Citrate Anticoagulation With Fixed Dose Versus Adjusted Citrate Program
A Phase 4 study testing fixed citrate doses protocol and adjusted citrate doses protocol in people with Critical Illness and Kidney Replacement Disorder, run by Peking Union Medical College Hospital at 1 site in China.
Trial 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 . Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Kidney Replacement Disorder, Coagulation; Intravascular
- What is being tested?
- fixed citrate doses protocol and adjusted citrate doses protocol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteChina
- Study dates
- Aug 2015to May 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients older than 18 years of age who required CVVH were consecutively screened
Who cannot join
- Requiring extracorporeal membrane oxygenation (ECMO) at the time of hemofiltration, insufficient data available or missing and running time less than 6 hours
Trial locations and contacts
1 site in 1 country.
China1 site
MICU of Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
About this study
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
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.
Read the 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.
- Being tested
- fixed citrate doses protocol, adjusted citrate doses protocol
- Keywords
- Regional citrate anticoagulation, Protocol, Filter lifespan
- Medical subject headings
- Critical Illness, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fixed citrate doses protocolOther
Also called fixed citrate circuit concentration protocol
fixed doses of anticoagulant citrate dextrose solution to meet a circuit citrate concentration of 4 mmol/l.
adjusted citrate doses protocolOther
the starting infusion rate of anticoagulant citrate dextrose solution be set 2.5 % of blood flow and then be adjusted to obtain postfilter ionized calcium levels of less than 0.40 mmol/l.
| Study group | Role | What they receive |
|---|---|---|
| fixed citrate doses protocol | Experimental | Fixed citrate doses protocol: Anticoagulant Citrate Dextrose Solution ( Na+ 224, citrate 113, bicarbonate 203mmol/l, Fresenius Kabi, Italy) was administered in the prefilter ahead of the blood pump, which was set to meet a circuit citrate concentration of 4 mmol/l (duration: the maximum time is 72 hrs). Receives: Other: fixed citrate doses protocol |
| adjusted citrate doses protocol | Active comparator | Adjusted citrate doses protocol: Anticoagulant Citrate Dextrose Solution ( Na+ 224, citrate 113, bicarbonate 203mmol/l, Fresenius Kabi, Italy) was administered in the prefilter ahead of the blood pump, which the starting infusion rate be set 2.5 % of blood flow ( dosage range: 160-250ml/h) and then be adjusted to obtain postfilter ionized calcium levels of less than 0.40 mmol/l (duration: the maximum time is 72 hrs. ) Receives: Other: adjusted citrate doses protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
the survival time of the first filter due to unexpected disconnection
The interval (hours) of the installation and replacement of the first filter. The unexpected disconnection defined as filter clotting more than two grades or transmembranous pressure across the circuit exceeded >300 mmHg. The filters were changed routinely after 72 hours of CVVH treatment, so maximum survival time of the filter was recorded as 72 hrs.
Measured: the time period on CVVH, maximum 72 hour
Secondary outcomes (5)
the overall survival time of the first filter
The interval (hours) of the installation and replacement of the first filter. The survival time derived from analysis of CVVH stopping for any cause. The reasons for CVVH stopping included unexpected disconnection (defined as filter clotting more than two grades or transmembranous pressure across the circuit exceeded >300 mmHg) and expected disconnection (such as scheduled, catheter malfunction, death or discharge, metabolic complications).The filters were changed routinely after 72 hours of CVVH treatment, so maximum survival time of the filter was recorded as 72 hrs.
Measured: the time period on CVVH, maximum 72 hour
the frequency of change in the infusion pump rate of calcium gluconate 10% Injection
recorded the change frequency (times per patient per hour ) in calcium gluconate infusion pump during the treatment period. Data were collected from records of the daily prescriptions.
Measured: the time period on CVVH, maximum 72 hour
the frequency of change in the infusion pump rate of Sodium Bicarbonate 5% Injection
recorded the change frequency (times per patient per hour) in bicarbonate infusion pump during the treatment period. Data were collected from records of the daily prescriptions.
Measured: the time period on CVVH, maximum 72 hour
the frequency of change in the infusion pump rate of Anticoagulant Citrate Dextrose Solution
recorded the change frequency (times per patient per hour ) in citrate infusion pump during the treatment period. Data were collected from records of the daily prescriptions.
Measured: the time period on CVVH, maximum 72 hour
incidences of severe metabolic disorders
defined as metabolic alkalosis with blood's pH value >7.5, metabolic acidosis with blood's pH value < 7.25, hypocalcemia with ionized calcium < 0.7 mmol/L, hypercalcemia with total serum calcium ≥ 2.75mmol/L, hypernatremia with Na+ ≥ 150mmol/L), bleeding disorders (defined as the decline of hemoglobin 10g/l within 12 hours) and suspected citrate accumulation was identified as a total calcium/ionic calcium index ≥ 2.5
Measured: the time period on CVVH, maximum 72 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2016 (estimated)
- Study startAug 2015
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bin Du, Prof., Principal investigator, Department of medical ICU,Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02663960
- Sponsor's protocol ID
- ZS-950
- Status last verified
- Aug 2016
- First submitted
- 3 Jan 2016
- Last updated
- 16 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 33784963
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02663960
- Acronym / sponsor ID
- ZS-950
- Keywords
- Regional citrate anticoagulation, Protocol, Filter lifespan
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- Aug 2015
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 26 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| fixed citrate doses protocol | Experimental | Other: fixed citrate doses protocolFixed citrate doses protocol: Anticoagulant Citrate Dextrose Solution ( Na+ 224, citrate 113, bicarbonate 203mmol/l, Fresenius Kabi, Italy) was administered in the prefilter ahead of the blood pump, which was set to meet a circuit citrate concentration of 4 mmol/l (duration: the maximum time is 72 hrs). |
| adjusted citrate doses protocol | Active comparator | Other: adjusted citrate doses protocolAdjusted citrate doses protocol: Anticoagulant Citrate Dextrose Solution ( Na+ 224, citrate 113, bicarbonate 203mmol/l, Fresenius Kabi, Italy) was administered in the prefilter ahead of the blood pump, which the starting infusion rate be set 2.5 % of blood flow ( dosage range: 160-250ml/h) and then be adjusted to obtain postfilter ionized calcium levels of less than 0.40 mmol/l (duration: the maximum time is 72 hrs. ) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients older than 18 years of age who required CVVH were consecutively screened
Key exclusion criteria (1 listed)
- Requiring extracorporeal membrane oxygenation (ECMO) at the time of hemofiltration, insufficient data available or missing and running time less than 6 hours
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fixed citrate doses protocolAlso: fixed citrate circuit concentration protocolfixed doses of anticoagulant citrate dextrose solution to meet a circuit citrate concentration of 4 mmol/l. | Other | fixed citrate doses protocol |
| adjusted citrate doses protocolthe starting infusion rate of anticoagulant citrate dextrose solution be set 2.5 % of blood flow and then be adjusted to obtain postfilter ionized calcium levels of less than 0.40 mmol/l. | Other | adjusted citrate doses protocol |
Primary outcome
the survival time of the first filter due to unexpected disconnection
Time frame: the time period on CVVH, maximum 72 hour
The interval (hours) of the installation and replacement of the first filter. The unexpected disconnection defined as filter clotting more than two grades or transmembranous pressure across the circuit exceeded >300 mmHg. The filters were changed routinely after 72 hours of CVVH treatment, so maximum survival time of the filter was recorded as 72 hrs.
5 secondary outcomes
the overall survival time of the first filter
Time frame: the time period on CVVH, maximum 72 hour
the frequency of change in the infusion pump rate of calcium gluconate 10% Injection
Time frame: the time period on CVVH, maximum 72 hour
the frequency of change in the infusion pump rate of Sodium Bicarbonate 5% Injection
Time frame: the time period on CVVH, maximum 72 hour
the frequency of change in the infusion pump rate of Anticoagulant Citrate Dextrose Solution
Time frame: the time period on CVVH, maximum 72 hour
incidences of severe metabolic disorders
Time frame: the time period on CVVH, maximum 72 hour
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
- Derived from this study: PubMed 33784963Shi 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bin Du, Prof. principal investigator
Department of medical ICU,Peking Union Medical College Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing fixed citrate doses protocol and adjusted citrate doses protocol in people with Critical Illness and Kidney Replacement Disorder, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the survival time of the first filter due to unexpected disconnection (time frame: the time period on CVVH, maximum 72 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02663960, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2020.