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Prevention of Dysrhythmias on the Cardiac Intensive Care Unit - Does Maintenance of High-normal Serum Potassium Levels Matter (TIGHT-K)

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ClinicalTrials.gov Identifier: NCT04053816
Recruitment Status : Not yet recruiting
First Posted : August 13, 2019
Last Update Posted : August 19, 2019
Sponsor:
Collaborator:
London School of Hygiene and Tropical Medicine
Information provided by (Responsible Party):
Barts & The London NHS Trust

Tracking Information
First Submitted Date  ICMJE August 9, 2019
First Posted Date  ICMJE August 13, 2019
Last Update Posted Date August 19, 2019
Estimated Study Start Date  ICMJE October 2019
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 12, 2019)
The presence of new onset AF until 120 hours after surgery or discharge from hospital, whichever is sooner [ Time Frame: Maximum of 5 days ]
Episode of AF lasting ≥30 seconds that is both clinically detected and electrocardiographically confirmed (on either a 12-lead electrocardiogram (ECG), telemetry or Holter monitoring
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04053816 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2019)
  • Prevalence of all AF including those identified on holter monitors [ Time Frame: Maximum of 5 days ]
    All episodes of AF detected on ECG and or holter monitor until 120 hours after surgery or discharge from hospital, whichever is sooner
  • Prevalence of all other non-AF dysrhythmias, defined using standard diagnostic criteria [ Time Frame: Maximum of 5 days ]
    All non-AF dysrhythmias detected on ECG and or holter monitor until 120 hours after surgery or discharge from hospital, whichever is sooner
  • In-patient mortality [ Time Frame: Maximum 6 months ]
    Number of patients deceased during their hospital stay
  • 6-month mortality [ Time Frame: 6 months ]
    All incidence of mortality during hospital stay and follow up
  • Critical care length of stay [ Time Frame: Maximum 6 months ]
    Number of days patients are in ICU
  • Hospital length of stay [ Time Frame: Maximum 6 months ]
    Number of days patients are inpatients in all hospital wards
  • Costs relating to potassium therapy [ Time Frame: Maximum of 5 days ]
    Financial cost of administering potassium therapy to patients
  • Quality of life at 6 months: questionnaire [ Time Frame: 6 months ]
    Quality of life questionnaire(EQ-5D-5L) administered before surgery and at 6 month follow up
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prevention of Dysrhythmias on the Cardiac Intensive Care Unit - Does Maintenance of High-normal Serum Potassium Levels Matter
Official Title  ICMJE The TIGHT-K STUDY. Prevention of Dysrhythmias on the Cardiac Intensive Care Unit - Does Maintenance of High-normal Serum Potassium Levels Matter
Brief Summary The purpose of this study is to determine whether maintaining serum potassium levels at ≥3.6 mEq/L is non-inferior to normal treatment (≥4.5 mEq/L) on the occurrence of new onset atrial fibrillation (AF) dysrhythmia post-surgery in patients undergoing isolated coronary artery bypass graft (CABG) surgery.
Detailed Description

At least one in three patients is affected by atrial fibrillation (AF) after cardiac surgery, with most episodes occurring in the first five postoperative days. AF occurrence is associated with increased morbidity, short and long-term mortality, intensive care unit (ICU) and hospital stay and cost of care. Persistence of these associations after adjustment for potential confounding factors suggests that they may be causal. The incidence and prevalence of AF and its associated costs are expected to increase as the surgical population ages. Extensive effort is undertaken to prevent AF after cardiac surgery from occurring, but clinical practice in this area is highly variable and the evidence base for most interventions is sparse.

Potassium plays an important role in cardiac electrophysiology. Serum potassium concentrations ([K+]) are commonly low following cardiac surgery, and appear marginally lower in those suffering atrial arrhythmias in non-surgical cohorts. Despite an absence of proof that this association is causal, efforts to maintain serum [K+] in the 'high-normal' range (≥ 4.5 mEq/L), as opposed to just intervening if potassium drops below its lower 'normal' threshold (<3.6 mEq/L), are considered 'routine practice' for AF prevention in post-surgical patients in many centres across the world.

From the (unpublished) data from our Tight-K Feasibility Study, all 160 patients would have required at least one dose of potassium to supplement their levels to this high-normal range and 45.5% of all serum [K+] measurements were below 4.5mEq/L at some point. Data from the same pilot study show a median number of potassium doses given in the 'tight' group (high-normal serum potassium target) of seven, compared to a median of one, with most patients not receiving any potassium supplementation at all, in the 'relaxed' group. This demonstrated for the first time ever, that the practice does achieve a separation in serum potassium levels between the two groups, so the protocol is indeed effective in achieving higher serum potassium levels.

The efficacy of the practice of maintaining high-normal serum potassium levels for the prevention of AF after cardiac surgery, however, remains unproven and data supporting it are extremely limited, being derived from observational studies rather than randomised trials. Indeed, no data exist to demonstrate that maintaining a high-normal potassium level is beneficial in these circumstances, or that aggressive replenishment of potassium in these patients improves outcome.

Meanwhile, potassium supplementation may cause discomfort or harm. Routine central venous potassium administration in the early post-operative period, when oral supplementation is not possible, is time-consuming, costly and associated with clinical risk: rapid infusion can prove fatal, and leaving central venous catheters in situ for the sole purpose of potassium replacement increases infection risk. Oral replacement (when feasible) is commonly associated with profound nausea and gastrointestinal side effects, and is very poorly tolerated by patients. The annual costs of intravenous potassium exceed those for other drugs in many cardiac surgical units due to the large quantities administered. Nursing time (e.g. for drug checks and administration) will add to this cost.

The routine maintenance of serum [K+] ≥ 4.5 mEq/L is a costly practice of unproven efficacy that is unpleasant and may be hazardous for patients. The investigators shall address this issue, performing the first appropriately powered non-inferiority multicentre randomised trial of potassium supplementation in patients undergoing coronary artery bypass surgery.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Arrhythmias, Cardiac
Intervention  ICMJE Drug: Potassium

The trial treatment will start when patients are admitted to the intensive care unit after their surgery. The patient will undergo regular blood investigations, as per current practice. The frequency of K+ monitoring while on ICU will be according to clinician / nursing staff preference.

Potassium supplementation will be according to local hospital protocols. This can be either via an intravenous infusion or as a tablet. Patients will otherwise be treated as per current hospital protocol.

Study Arms  ICMJE
  • Experimental: Relaxed control
    Those randomised to the 'Relaxed' Group will receive potassium supplementation only if their serum potassium drops below or equals 3.6 mEq/L.
    Intervention: Drug: Potassium
  • Active Comparator: Tight control
    Patients randomised to the 'Tight' group will receive potassium supplementation if their serum potassium falls below 4.5 mEq/L (current practice).
    Intervention: Drug: Potassium
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 12, 2019)
1684
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2022
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

- Undergoing isolated CABG surgery

Exclusion Criteria:

  • Age <18
  • Previous AF
  • Ongoing infection/sepsis at the time of recruitment
  • Pre-operative high-degree atrioventricular block
  • Pre-operative serum K+ >5.5 mEq/L
  • Current/previous use of medication for the purposes of cardiac rhythm management
  • Dialysis-dependent end-stage renal failure
  • Concurrent patient involvement in another clinical trial assessing cardiac rhythm post-operative interventions
  • Unable to give informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Professor Ben O'Brien 020 7958 8231 Ben.Obrien@bartshealth.nhs.uk
Contact: Ruth Canter 020 7927 2071 ruth.canter@lshtm.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04053816
Other Study ID Numbers  ICMJE 260639
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Barts & The London NHS Trust
Study Sponsor  ICMJE Barts & The London NHS Trust
Collaborators  ICMJE London School of Hygiene and Tropical Medicine
Investigators  ICMJE Not Provided
PRS Account Barts & The London NHS Trust
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP