Citrate 4% Versus Heparinised Saline in Preventing Peripherally Inserted Central Catheter (PICC) Occlusions

Study Overview
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Brief Summary
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This study is a prospective, randomized, non-blinded study. 1 group will be assigned the standard arm with use of heparinised saline (10U/ml) lock in between each catheter use. This is consistent with the standard procedure of PICC care in the investigators' centre. The second group will be assigned the intervention with use of 4% citrate lock (Dirinco Citra-Lock 4%) in between each catheter use.

Detailed Description
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PICC occlusion in patients requiring long-term central line access for chemotherapy is a recurrent issue. Occlusion is usually managed by administration of fibrinolytic agents, and subsequent removal and re-insertion if unsuccessful. Locally, the current clinical practice is to use heparinised saline at a concentration of 10U/ml as a locking agent in between use of the PICC line to prevent occlusion. Citrate 4% has antithrombotic and antibacterial properties, which makes it potentially superior to heparin as a locking agent. Citrate chelates ionised calcium in blood, inhibiting calcium-dependent clotting pathways. Also, as a chelating agent, it results in inhibition of growth of micro-organisms. Citrate-based anticoagulation is often preferred over heparin because of its safety and rapid systemic clearance. Citrate also is safe for heparin induced thrombocytopenia patients. The effects of each agent have been compared in renal patients with central lines on haemodialysis. These studies have demonstrated that 4% citrate is at least equivalent (MacRae, 2008) or even superior (Grudzinski, 2007) to heparin 5000U/ml in preventing catheter occlusions, and superior in preventing infection (Weijmer, 2002). This study is a prospective, randomized, non-blinded study. 1 group will be assigned the standard arm with use of heparinised saline (10U/ml) lock in between each catheter use. This is consistent with the standard procedure of PICC care in the investigators' centre. The second group will be assigned the intervention with use of 4% citrate lock (Dirinco Citra-Lock 4%) in between each catheter use. Patients will be followed for up to 6 months or until the catheter is removed, or until the study ends. A standardised data tracking form will be used to assess baseline characteristics as well as number of times urokinase was used. Nursing documentation regarding each PICC flushing (standard documentation as per hospital protocol) will be evaluated for number of discrete attempts made to troubleshoot lines without use of urokinase. Positive blood culture results will be recorded for each patient.

Official Title
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Citrate 4% Versus Heparinised Saline in Preventing Peripherally Inserted Central Catheter (PICC) Occlusions

Conditions
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Occlusion

Intervention / Treatment
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* Drug: Citrate 4%
* Drug: Heparinised saline (10U/ml)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age more than or equal to 21 years. Histologic or cytologic diagnosis of haematological or oncological malignancy Signed informed consent from patient or legal representative Patients on antiplatelet therapy may be recruited to the study Exclusion Criteria: Pregnancy. Anticoagulation - warfarin or heparin or novel oral anticoagulants Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: heparin 10U/ml<br>Heparinised saline (10U/ml) lock in between each catheter use (with standard twice weekly normal saline flushing if catheter not being used) | Drug: Heparinised saline (10U/ml)<br>* In patients randomised to the heparinised saline arm, the PICC line will be locked with 10U/ml heparinised saline between each use. Lines will also be flushed with 20ml of normal saline and locked with the locking agent twice a week, if the time elapsed between each use is more than one week. This is part of the standard local protocol. Patients will be followed for up to 6 months or until the catheter is removed, or until the study ends<br>|
| Experimental: citrate 4%<br>4% citrate lock in between each catheter use (with standard twice weekly normal saline flushing if catheter not being used) | Drug: Citrate 4%<br>* In patients randomised to the citrate arm, the PICC line will be locked with a total of 1.6ml of citrate 4% (0.8ml per lumen in a double-lumen PICC), between each use. Lines will also be flushed with 20ml of normal saline and locked with the locking agent twice a week, if the time elapsed between each use is more than one week. This is part of the standard local protocol. Patients will be followed for up to 6 months or until the catheter is removed, or until the study ends<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of catheter occlusion | Compare the rates of catheter occlusion in patients who receive citrate 4% as a locking agent, versus those who receive heparinised saline (10U/ml). | From post insertion to 6 months or until the catheter is removed, whichever is earlier. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Line troubleshooting | to compare the time to requiring troubleshooting of the line but not amounting to urokinase use | From post insertion to 6 months or until the catheter is removed, whichever is earlier. | 
| Catheter associated bacteraemia | to compare the time to development of catheter associated bacteraemia | From post insertion to 6 months or until the catheter is removed, whichever is earlier. | 
| Bleeding complications | to compare the time to development of bleeding complications, either local or systemic. | From post insertion to 6 months or until the catheter is removed, whichever is earlier. |