Hydrochloric Acid Lock Therapy in Children With Cancer

Sponsor

Rigshospitalet, Denmark (Other)

Overall Status

Recruiting

CT.gov ID

NCT05376566

Collaborator

Odense University Hospital (Other), Aarhus University Hospital Skejby (Other)

100

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Aim: This study will test whether treatment of central line associated bloodstream infection (CLABSI) with hydrochloric acid lock therapy (HALT) can significantly reduce the risk of treatment failure (comprising failure to clear initial infection, relapse or reinfection) in children and adolescents treated for cancer.

Study design: A multicenter, double-blind, randomized controlled trial.The assignment is parallel, with cross-over in case of reinclusion of the patient.

Patients and randomisation: A target population of 100 children and adolescents treated for cancer will be enrolled within 48 hours after detection of a positive blood culture/CLABSI.

They will be randomized as followed:

Intervention group: HALT.
Control group: Normal saline (placebo).

In addition to the study intervention, participants in both arms will receive standard systemic antibiotic therapy according to the preference of the ward clinician.

Condition or Disease	Intervention/Treatment	Phase
Central Line-associated Bloodstream Infection (CLABSI)	Drug: Hydrochloric Acid (2 M) Drug: Normal saline	N/A

Detailed Description

BACKGROUND

Patients with cancer and a long-term central venous access device (CVAD), including tunneled lines and ports, are at risk of developing central line-associated bloodstream infections (CLABSI). A patient with CLABSI is treated with systemic antibiotic therapy. Additionally, prompt removal of CVAD because of CLABSI is often recommended. However, removal and replacement of long-term CVAD in children and adolescents with cancer is often highly complicated due to limited vascular access, refractory thrombocytopenia, or critical need for central access, and thus CVAD-salvage is attempted. In Denmark, hydrochloric acid lock therapy (HALT) has been used routinely to all children and adolescents with cancer and CLABSI. However, HALT is not recommended outside Denmark due to limited evidence of its use.

PATIENT AND METHODS

Eligible patients with CLABSI (defined as a laboratory-confirmed bloodstream infection, not secondary to infection at another site, in a patient who has a CVAD) will be enrolled within 48 hours after detection of a positive blood culture/CLABSI and randomized to receive blinded lock therapy with hydrochloric acid (2 M) or placebo (normal saline). HALT and placebo lock therapy is carried out by trained oncologic nurses in identical fashion: Hydrochloric acid or normal saline in a volume corresponding to dead space (0.3-1.0ml) will be instilled and aspirated 10 min later; the instillation is completed 3 times. In addition to the study intervention, participants in both arms will receive standard systemic antibiotic therapy according to the preference of the ward clinician.

The patient is followed 6 weeks from instillation with HALT/placebo. The patient will be re-included if the patient has a CLABSI later than 6 weeks from a previous CLABSI. In case of re-inclusion the patient will cross over to the opposite group (intervention/HALT or placebo/normal saline respectively).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel assignment with cross-over allocation for reincluded patients.Parallel assignment with cross-over allocation for reincluded patients.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

The study will be blinded using masked vial containing either hydrochloric acid or normal saline and coloured syringes. All masked vials have a unique three-figure randomization code.

Primary Purpose:

Treatment

Official Title:

Hydrochloric Acid Lock Therapy for Central Line-associated Infections in Children With Cancer

Actual Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

May 31, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intervention group Hydrochloric acid (2 M)	Drug: Hydrochloric Acid (2 M) Hydrochloric acid (2 M) in a volume corresponding to dead space (0.3-1.0 ml) will be instilled and aspirated 10 min later; the instillation is completed 3 times. Other Names: Intervention
Placebo Comparator: Control group Normal saline	Drug: Normal saline Normal saline in a volume corresponding to dead space (0.3-1.0 ml) will be instilled and aspirated 10 min later; the instillation is completed 3 times. Other Names: Placebo

Arm

Intervention/Treatment

Active Comparator: Intervention group

Hydrochloric acid (2 M)

Drug: Hydrochloric Acid (2 M)

Hydrochloric acid (2 M) in a volume corresponding to dead space (0.3-1.0 ml) will be instilled and aspirated 10 min later; the instillation is completed 3 times.

Other Names:

Intervention

Placebo Comparator: Control group

Normal saline

Drug: Normal saline

Normal saline in a volume corresponding to dead space (0.3-1.0 ml) will be instilled and aspirated 10 min later; the instillation is completed 3 times.

Other Names:

Placebo

Outcome Measures

Primary Outcome Measures

Treatment failure. [Within 6 weeks after HALT or placebo (normal saline) treatment of the CVAD.]
Defined as 1) persistent infection (persistent positive blood cultures for more than 48 h) or relapse (a new CLABSI with an identical bacterial isolate), 2) a new CLABSI with any bacterial isolate, 3) infection-related removal of central access device (CVAD), 4) infection-related death. The treatment group comparison will be based on a test of the risk ratio between the two groups.

Other Outcome Measures

Safety outcome 1: Infusion-related reactions i.e. anaphylactic shock, pain, rash or sensory disturbances. [Within 24 hours after start of HALT or placebo (normal saline) treatment of the CVAD.]
Incidence will be tabulated as number of events and number of patients experiencing an event according to current actual treatment.
Safety outcome 2: Death or admission to Pediatric Intensive Care Unit associated to infection [Within 6 weeks after HALT or placebo (normal saline) treatment of the CVAD.]
Incidence will be tabulated as number of events, number of patients experiencing the event, and number of events per person-year of observation. Data will be categorized according to current actual treatment.
Safety outcome 3: Mechanical catheter damage or catheter occlusion requiring thrombolytic therapy. [Within 6 weeks after HALT or placebo (normal saline) treatment of the CVAD.]
Incidence will be tabulated as number of events and number of patients experiencing an event according to current actual treatment.
Exploratory outcome 1: Number of days with antibiotic treatment. [[Time Frame: Within 6 weeks after HALT or placebo (normal saline)]]
Number of days the child was prescribed antibiotic treatment within 6 weeks after admission with CLABSI.
Exploratory outcome 2: Treatment failure [Time Frame: Within 6 weeks after HALT or placebo (normal saline)]
Defined as 1) persistent infection (persistent positive blood cultures for more than 48 h) or relapse (a new CLABSI with an identical bacterial isolate), 2) a new CLABSI with any bacterial isolate, 3) infection-related removal of central access device (CVAD), 4) infection-related death, 5) antibiotic treatment due to suspicion of infection despite lack of positive blood culture The treatment group comparison will be based on a test of the risk ratio between the two groups.

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients aged 0-17 years. NB, In case of slow recruitment, patients aged 17-30 years will also be included.
Patients receiving treatment for cancer (any type and at any point in the course of the disease).
CVAD in situ (port-a-cath and all central lines incl. PICC-line catheter).
New diagnosis of CLABSI (defined as a laboratory-confirmed bloodstream infection, not secondary to infection at another site, in a patient who has a CVAD). NB, patients who had a CLABSI prior to the beginning of the study are accepted for enrollment if they have a new CLABSI during the patient enrollment phase.

Participants are followed for 6 weeks from HALT/placebo. In case of a CLABSI later than 6 weeks from a previous CLABSI, the patient will be re-included in the opposite group (cross-over allocation for reincluded patients).

Exclusion Criteria:

Plan to remove CVAD within 6 days.
Instantly admission to Intensive Care Unit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital	Aarhus		Denmark	3200
2	Department of Paediatrics and Adolescent Medicine, Odense University Hospital	Odense		Denmark	4000