Arrhythmias, CardiacPhase 3TIGHT-KNCT04053816
Prevention of Dysrhythmias on the Cardiac Intensive Care Unit - Does Maintenance of High-normal Serum Potassium Levels Matter
A Phase 3 study testing Potassium in people with Arrhythmias, Cardiac, run by Barts & The London NHS Trust at 1 site in United Kingdom.
Trial summary
The purpose of this study is to determine whether a strategy of maintaining serum potassium levels at ≥3.6 mEq/L is non-inferior to a strategy of usual treatment (≥4.5 mEq/L) on the occurrence of new onset atrial fibrillation after cardiac surgery (AFACS) in patients undergoing isolated coronary artery bypass graft… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arrhythmias, Cardiac
- What is being tested?
- Potassium
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,684 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Oct 2020to 26 Jun 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Scheduled to have isolated CABG surgery
- Patient in sinus rhythm
Who cannot join
- Age less than 18 years
- Previous history of Atrial Fibrillation, Atrial Flutter and/or Atrial Tachyarrhythmia
- Pre-operative high-degree atrioventricular (AV) block (defined as Mobitz type 2 second degree AV block or complete heart block)
- Pre-operative serum [K+] greater than 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The TIGHT-K STUDY. Prevention of Dysrhythmias on the Cardiac Intensive Care Unit - Does Maintenance of High-normal Serum Potassium Levels Matter
The purpose of this study is to determine whether a strategy of maintaining serum potassium levels at ≥3.6 mEq/L is non-inferior to a strategy of usual treatment (≥4.5 mEq/L) on the occurrence of new onset atrial fibrillation after cardiac surgery (AFACS) in patients undergoing isolated coronary artery bypass graft (CABG) surgery.
Read the detailed description
At least one in three patients is affected by atrial fibrillation after cardiac surgery(AFACS), 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.
- Conditions
- Arrhythmias, Cardiac
- Being tested
- Potassium
- Keywords
- cardiovascular, potassium supplementation, cardiac surgery, atrial fibrillation, coronary artery bypass grafting, potassium
- Medical subject headings
- Arrhythmias, Cardiac, Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PotassiumDrug
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 group | Role | What they receive |
|---|---|---|
| Relaxed control | Experimental | Those randomised to the 'Relaxed' Group will receive potassium supplementation only if their serum potassium drops below 3.6 mEq/L. Receives: Drug: Potassium |
| Tight control | Active comparator | Patients randomised to the 'Tight' group will receive potassium supplementation if their serum potassium falls below 4.5 mEq/L (current practice). Receives: Drug: Potassium |
What is being measured
The primary outcome is the main question the study is designed to answer.
The presence of new onset AFACS until until hour 120 after initial admission to ICU/post-operative care facility, or discharge from hospital, whichever occurs first.
Episode of AFACS lasting ≥30 seconds that is both clinically detected and electrocardiographically confirmed (on either a 12-lead electrocardiogram (ECG), telemetry or Holter monitoring
Measured: Maximum of 5 days
Secondary outcomes (9)
The incidence of new onset AFACS
Detected on Holter monitor until hour 120 after initial admission to ICU/post-operative care facility or discharge from hospital, whichever occurs first.
Measured: Maximum of 5 days
The incidence of at least one episode of AFACS
Clinically identified AFACS or Holter-identified AFACS until hour 120 after initial admission to ICU/post-operative care facility or discharge from hospital, whichever occurs first.
Measured: Maximum of 5 days
Number of patients experiencing at least one episode of a non-AF arrhythmia.
Identified on Holter monitor until hour 120 after after initial admission to ICU/post-operative care facility or discharge from hospital, whichever occurs first
Measured: Maximum of 5 days
In-patient mortality
Measured: Maximum 6 months
6-month mortality
Measured: Maximum 6 months
Critical care length of stay
Number of days patients are in inpatients in critical care
Measured: Maximum 6 months
Hospital length of stay
Number of days patients are inpatients in all hospital wards
Measured: Maximum 6 months
Costs relating to potassium therapy
Financial cost of administering potassium therapy to patients
Measured: Maximum of 5 days
Quality of life at 6 months: questionnaire
Quality of life questionnaire(EQ-5D-5L) administered before surgery and at 6 month follow up
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2019
- Study start20 Oct 2020
- Primary completion22 Nov 2023
- Study completion26 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Arrhythmias, CardiacStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,684 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barts & The London NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- London School of Hygiene and Tropical Medicine, Aberdeen Royal Infirmary, Mid and South Essex NHS Foundation Trust, Blackpool Victoria Hospital, University Hospitals Bristol and Weston NHS Foundation Trust, Hull University Teaching Hospitals NHS Trust, Derriford Hospital, Deutsches Herzzentrum der Charité, Freeman Health System, Golden Jubilee National Hospital, Guy's and St Thomas' NHS Foundation Trust, Hammersmith Hospitals NHS Trust, Oxford University Hospitals NHS Trust, King's College Hospital NHS Trust, The Leeds Teaching Hospitals NHS Trust, Liverpool Heart and Chest Hospital NHS Foundation Trust, Sheffield Teaching Hospitals NHS Foundation Trust, Nottingham University Hospitals NHS Trust, Royal Infirmary of Edinburgh, Royal Sussex County Hospital, St George's University Hospitals NHS Foundation Trust, Universität Münster, Wythenshawe Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04053816
- Sponsor's protocol ID
- 260639
- Acronym
- TIGHT-K
- Status last verified
- Nov 2024
- First submitted
- 9 Aug 2019
- Last updated
- 5 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
O'Brien B, Campbell NG, Allen E, Jamal Z, Sturgess J, Sanders J, Opondo C, Roberts N, Aron J, Maccaroni MR, Gould R, Kirmani BH, Gibbison B, Kunst G, Zarbock A, Kleine-Bruggeney M, Stoppe C, Pearce K, Hughes M, Van Dyck L, Evans R, Montgomery HE, Elbourne D; TIGHT K investigators. Potassium Supplementation and Prevention of Atrial Fibrillation After Cardiac Surgery: The TIGHT K Randomized Clinical Trial. JAMA. 2024 Sep 24;332(12):979-988. doi: 10.1001/jama.2024.17888.
PubMed 39215972Campbell NG, Allen E, Evans R, Jamal Z, Opondo C, Sanders J, Sturgess J, Montgomery HE, Elbourne D, O'Brien B. Impact of maintaining serum potassium concentration >/= 3.6mEq/L versus >/= 4.5mEq/L for 120 hours after isolated coronary artery bypass graft surgery on incidence of new onset atrial fibrillation: Protocol for a randomized non-inferiority trial. PLoS One. 2024 Mar 13;19(3):e0296525. doi: 10.1371/journal.pone.0296525. eCollection 2024.
PubMed 38478488
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The TIGHT-K STUDY. Prevention of Dysrhythmias on the Cardiac Intensive Care Unit - Does Maintenance of High-normal Serum Potassium Levels Matter
- ClinicalTrials.gov ID
- NCT04053816
- Acronym / sponsor ID
- TIGHT-K / 260639
- Conditions
- Arrhythmias, Cardiac
- Keywords
- cardiovascular, potassium supplementation, cardiac surgery, atrial fibrillation, coronary artery bypass grafting, potassium
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,684 participants (actual)
- Lead sponsor
- Barts & The London NHS TrustUniversity, hospital or other
- Collaborators
- London School of Hygiene and Tropical Medicine, Aberdeen Royal Infirmary, Mid and South Essex NHS Foundation Trust, Blackpool Victoria Hospital, University Hospitals Bristol and Weston NHS Foundation Trust, Hull University Teaching Hospitals NHS Trust, Derriford Hospital, Deutsches Herzzentrum der Charité, Freeman Health System, Golden Jubilee National Hospital, Guy's and St Thomas' NHS Foundation Trust, Hammersmith Hospitals NHS Trust, Oxford University Hospitals NHS Trust, King's College Hospital NHS Trust, The Leeds Teaching Hospitals NHS Trust, Liverpool Heart and Chest Hospital NHS Foundation Trust, Sheffield Teaching Hospitals NHS Foundation Trust, Nottingham University Hospitals NHS Trust, Royal Infirmary of Edinburgh, Royal Sussex County Hospital, St George's University Hospitals NHS Foundation Trust, Universität Münster, Wythenshawe Hospital
- Study start
- 20 Oct 2020 (actual)
- Primary completion
- 22 Nov 2023 (actual)
- Study completion
- 26 Jun 2024 (actual)
- First posted
- 13 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether a strategy of maintaining serum potassium levels at ≥3.6 mEq/L is non-inferior to a strategy of usual treatment (≥4.5 mEq/L) on the occurrence of new onset atrial fibrillation after cardiac surgery (AFACS) in patients undergoing isolated coronary artery bypass graft (CABG) surgery.
Detailed description
At least one in three patients is affected by atrial fibrillation after cardiac surgery(AFACS), 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Relaxed control | Experimental | Drug: PotassiumThose randomised to the 'Relaxed' Group will receive potassium supplementation only if their serum potassium drops below 3.6 mEq/L. |
| Tight control | Active comparator | Drug: PotassiumPatients randomised to the 'Tight' group will receive potassium supplementation if their serum potassium falls below 4.5 mEq/L (current practice). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Scheduled to have isolated CABG surgery
- Patient in sinus rhythm
Key exclusion criteria (8 listed)
- Age less than 18 years
- Previous history of Atrial Fibrillation, Atrial Flutter and/or Atrial Tachyarrhythmia
- Pre-operative high-degree atrioventricular (AV) block (defined as Mobitz type 2 second degree AV block or complete heart block)
- Pre-operative serum [K+] greater than 5.5 mEq/L
- Current/previous use of medication for the purposes of cardiac rhythm management
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PotassiumThe 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. | Drug | Relaxed control, Tight control |
Primary outcome
The presence of new onset AFACS until until hour 120 after initial admission to ICU/post-operative care facility, or discharge from hospital, whichever occurs first.
Time frame: Maximum of 5 days
Episode of AFACS lasting ≥30 seconds that is both clinically detected and electrocardiographically confirmed (on either a 12-lead electrocardiogram (ECG), telemetry or Holter monitoring
9 secondary outcomes
The incidence of new onset AFACS
Time frame: Maximum of 5 days
The incidence of at least one episode of AFACS
Time frame: Maximum of 5 days
Number of patients experiencing at least one episode of a non-AF arrhythmia.
Time frame: Maximum of 5 days
In-patient mortality
Time frame: Maximum 6 months
6-month mortality
Time frame: Maximum 6 months
Critical care length of stay
Time frame: Maximum 6 months
Hospital length of stay
Time frame: Maximum 6 months
Costs relating to potassium therapy
Time frame: Maximum of 5 days
Quality of life at 6 months: questionnaire
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2024.
- Results publication: PubMed 39215972O'Brien B, Campbell NG, Allen E, Jamal Z, Sturgess J, Sanders J, Opondo C, Roberts N, Aron J, Maccaroni MR, Gould R, Kirmani BH, Gibbison B, Kunst G, Zarbock A, Kleine-Bruggeney M, Stoppe C, Pearce K, Hughes M, Van Dyck L, Evans R, Montgomery HE, Elbourne D; TIGHT K investigators. Potassium Supplementation and Prevention of Atrial Fibrillation After Cardiac Surgery: The TIGHT K Randomized Clinical Trial. JAMA. 2024 Sep 24;332(12):979-988. doi: 10.1001/jama.2024.17888.
- Derived from this study: PubMed 38478488Campbell NG, Allen E, Evans R, Jamal Z, Opondo C, Sanders J, Sturgess J, Montgomery HE, Elbourne D, O'Brien B. Impact of maintaining serum potassium concentration >/= 3.6mEq/L versus >/= 4.5mEq/L for 120 hours after isolated coronary artery bypass graft surgery on incidence of new onset atrial fibrillation: Protocol for a randomized non-inferiority trial. PLoS One. 2024 Mar 13;19(3):e0296525. doi: 10.1371/journal.pone.0296525. eCollection 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Potassium in people with Arrhythmias, Cardiac, run by Barts & The London NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The presence of new onset AFACS until until hour 120 after initial admission to ICU/post-operative care facility, or discharge from hospital, whichever occurs first. (time frame: Maximum of 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04053816, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2024.