Condition category
Urological and Genital Diseases
Date applied
04/11/2017
Date assigned
08/11/2017
Last edited
10/07/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Haemodialysis is a method where blood is diverted to a machine to remove waste products and extra fluid that build up when the kidneys are not functioning properly. The drug heparin is normally used to stop haemodialysis circuits from clotting. When heparin cannot be used, the standard practice is to flush the circuit regularly with saline (salt water). This method is not well proven to stop circuit clotting. Clotted circuits mean unnecessary blood loss. Citrate has been used to stop circuit clotting (anticoagulation) for prolonged dialysis methods in Intensive Care. The aim of this study is to find out whether using citrate for short haemodialysis treatments is better than saline flushes at stopping clots in the circuit while also being safe.

Who can participate?
Hospital in-patients scheduled for at least two heparin-free hemodialysis sessions

What does the study involve?
Participants are randomly allocated to receive either citrate anticoagulation or standard heparin-free haemodialysis. At their next haemodialysis session they switch over to the alternate method. Blood tests are performed during and at the end of the citrate treatment sessions.

What are the possible benefits and risks of participating?
Citrate is known to be effective and works by lowering blood calcium so that clotting cannot take place. Low calcium levels can however be life threatening (e.g. heart arrhythmias). Citrate is infused into the blood only when it is outside the body to stop it from clotting when it goes through the dialysis circuit. Calcium is then infused back into this blood just before it re-enters the body so that the calcium levels remain normal. The risks are if not enough calcium is infused back into the body calcium levels become too low, but calcium levels are checked regularly to prevent this from happening.

Where is the study run from?
Khoo Teck Puat Hospital (Singapore)

When is the study starting and how long is it expected to run for?
April 2014 to July 2016

Who is funding the study?
Alexandra Health National Medical Research Centre (Singapore)

Who is the main contact?
Dr Terina Seow

Trial website

Contact information

Type

Scientific

Primary contact

Dr Terina Seow

ORCID ID

Contact details

Division of Renal Medicine
Department of General Medicine
Khoo Teck Puat Hospital
90 Yishun Central
Singapore
768828
Singapore

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Simple citrate anticoagulation protocol for low flux haemodialysis

Acronym

Study hypothesis

For patients unable to receive heparin anticoagulation during haemodialysis, saline flushes to reduce circuit clotting are often the norm. Regional citrate anticoagulation (RCA) although effective is not used by many centres including in Singapore. The aim of this study is to demonstrate the superiority and safety of a simple regional citrate anticoagulation regime, compared to saline flushes, for heparin-free low flux haemodialysis.

Ethics approval

National Health Group Domain Specific Research Board, 02/04/2015, ref: 2014/01037

Study design

Prospective open-label cross-over study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Haemodialysis

Intervention

Patients were allocated either to regional citrate anticoagulation or standard heparin free haemodialysis and subsequently cross over to the alternate method. The same cohort underwent both treatment arms (citrate and saline flushes) in consecutive haemodialysis sessions which would have been 48-72 hours apart. Citrate is 60-80% dialysed out immediately as it passes through the dialyser and the rest is metabolized by the body within minutes so no washout period is required. Blood tests were performed during and at the end of the citrate treatment sessions

Trisodium Citrate 13% or 500mM (Dirinco BV, Netherland) was infused at a fixed rate pre-filter (into the “heparin” line) according to blood flow (QB) as shown.

Trisodium Citrate 13% Infusion:
Blood flow Trisodium citrate 13%
150 ml/min 60ml/hour
200 ml/min 80ml/hour
250 ml/min 100ml/hour

Calcium Gluconate 10% (2.2 mmol Ca2+ in 10ml vial) was infused post filter (using a 3-way connector into the “venous” return line). Infusion rate was started at 70ml/hour. Calcium infusion rate is then adjusted to pre-filter iCa2+ level.

Calcium Gluconate 10% Infusion:
iCa2+ Level Calcium Gluconate Infusion
<0.65 mM Notify doctor. Terminate citrate infusion and change to heparin free
dialysis. Give 40 ml bolus over 30 mins
0.65-0.74 mM Give 20ml bolus over 30 mins and increase infusion by 20 ml/hr
0.75 – 0.9 mM Increase infusion by 20 ml/hr
0.91 – 1.2 mM Infuse at 70ml/hr
>1.2 mM Hold infusion for 30 mins and recheck

For the control arm, 100ml saline flushes were given per 30 minutes, extra flushes were allowed as per nurses’s discretion according to standard practice of monitoring for clots in the circuit.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

1. Thrombosis and circuit loss: at the end of the dialysis session, arterial and venous drip chambers and the filter were inspected by the nurse for visible signs of coagulation. A score of 1 (no clots), 2 (small clots), 3 (large clots) and 4 (complete clotting of circuit) was applied.
2. Anticoagulation achieved in citrate dialysis arm: post-filter iCa2+ (V) was tested at time 30, 60, 120 and 240 (just before ending) minutes.

Secondary outcome measures

Electrolytes and calcium levels for citrate dialysis arm: pre-filter iCa2+ levels (A) were measured at 0, 30, 60, 120 and 240 minutes. Electrolytes were sent to the lab at time 0 and 240 minutes.

Overall trial start date

01/04/2014

Overall trial end date

31/07/2016

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Hospital in-patients scheduled for at least 2 heparin-free hemodialysis sessions between August 2015-Jul 2016 at Khoo Teck Puat Hospital, Singapore
2. Haemoglobin >7.0g/dL
3. Haemodynamically stable
4. Reasonably functioning vascular access
5. Chronic haemodialysis patients and acute kidney injury patients

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

25

Participant exclusion criteria

1. Decompensated liver disease
2. Received blood products within last 24 hours/required blood products during the dialysis session
3. Haemostatic disorders or deranged clotting
4. Known allergy to citrate products

Recruitment start date

01/08/2015

Recruitment end date

31/07/2016

Locations

Countries of recruitment

Singapore

Trial participating centre

Khoo Teck Puat Hospital
768828
Singapore

Sponsor information

Organisation

Alexandra Health National Medical Research Centre

Sponsor details

Clinical Research Unit
Khoo Teck Puat Hospital
90 Yishun Central
Singapore
768828
Singapore

Sponsor type

Research council

Website

Funders

Funder type

Research council

Funder name

Alexandra Health National Medical Research Centre

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The trialists are submitting the results for publication in a peer-reviewed journal.

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Terina Seow once the study has been published. Consent from patient was obtained to permit data collected from the study to be allowed for use in future related studies. Data is anonymised. Research data and subject identifiers were stored separately.

Intention to publish date

31/12/2017

Participant level data

Available on request

Basic results (scientific)

Publication list

2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/29351783

Publication citations

Additional files

Editorial Notes

10/07/2018: Publication reference added.