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

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.

Study Overview

• Status: Unknown
• Conditions: Occlusion
• Intervention / Treatment: Drug: Heparinised saline (10U/ml); Drug: Citrate 4%

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • Nationa University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: heparin 10U/ml; 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); 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
Experimental: citrate 4%; 4% citrate lock in between each catheter use (with standard twice weekly normal saline flushing if catheter not being used)	Drug: Citrate 4%; 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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore

Publications and helpful links

General Publications

• Grudzinski L, Quinan P, Kwok S, Pierratos A. Sodium citrate 4% locking solution for central venous dialysis catheters--an effective, more cost-efficient alternative to heparin. Nephrol Dial Transplant. 2007 Feb;22(2):471-6. doi: 10.1093/ndt/gfl606. Epub 2006 Oct 25.
• Weijmer MC, Debets-Ossenkopp YJ, Van De Vondervoort FJ, ter Wee PM. Superior antimicrobial activity of trisodium citrate over heparin for catheter locking. Nephrol Dial Transplant. 2002 Dec;17(12):2189-95. doi: 10.1093/ndt/17.12.2189.
• Macrae JM, Dojcinovic I, Djurdjev O, Jung B, Shalansky S, Levin A, Kiaii M. Citrate 4% versus heparin and the reduction of thrombosis study (CHARTS). Clin J Am Soc Nephrol. 2008 Mar;3(2):369-74. doi: 10.2215/CJN.01760407.
• Strauss RG. Mechanisms of adverse effects during hemapheresis. J Clin Apher. 1996;11(3):160-4. doi: 10.1002/(SICI)1098-1101(1996)11:33.0.CO;2-9.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 31, 2017
• Primary Completion (Anticipated): July 31, 2018
• Study Completion (Anticipated): December 30, 2018

Study Registration Dates

• First Submitted: March 20, 2017
• First Submitted That Met QC Criteria: April 10, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): June 15, 2017
• Last Update Submitted That Met QC Criteria: June 14, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: 2016/01420

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No