糖尿病性ケトアシドーシスに対するバランスの取れた多電解質溶液と生理食塩水試験 (BEST-DKA)
中等度から重度の糖尿病性ケトアシドーシスを呈する患者のための輸液療法としてのバランスの取れた多電解質溶液と 0.9% 塩化ナトリウム
The goal of this blinded, cluster cross-over, randomised controlled trial is to determine whether fluid therapy with Plasma-Lyte® 148 increases the number of days alive and days out of hospital to day-28 compared to 0.9% sodium chloride ('0.9% saline') in critically ill patients presenting to the Emergency Department (ED) and deemed to require admission to a critical care area (ICU, HDU) with moderate to severe diabetic ketoacidosis (DKA).
調査の概要
詳細な説明
DKA is a life-threatening complication of diabetes mellitus, described in patients with both type-1 diabetes, and type-2 diabetes(1). Data from the Australian Institute of Health and Welfare suggest that between 2009-10 to 2014-15, there has been a 21% increase in the hospitalisation amongst young people with DKA(2). An interrogation of the Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcomes Research (CORE) database revealed that the incidence of ICU admission of patients with DKA in Australia and New Zealand increased 5-fold between 2000 and 2013 (0.97/100000, 95%CI 0.84 to1.10) in 2000 to (5.3/100000, 95%CI 4.98to 5.53, (P<0.0001)(3).
Increasing incidences were observed predominantly in rural and metropolitan hospitals (Figure 1), about 88% of the admissions to the ICU were from the ED. The median (IQR) ICU and hospital length of stay were 1.8 (1-2.8) and 4 (2.6-7.4) days respectively. Recent data from the ANZICS-CORE database confirmed the persistent high admission rate of severe DKA to Australian ICUs - 2849 and 2862 admissions in 2019 and 2020.
A major review of DKA management protocols in 2017 concluded that there are major deficiencies in evidence for optimal management of DKA(33). Current practice is guided by weak evidence and consensus opinion.
Studies comparing Plasma-Lyte® 148 vs. 0.9% saline in DKA demonstrate a trend towards a more rapid resolution of acidosis, equivalent glucose control and stable ketones with Plasma-Lyte® 148. In addition, there are trends towards reduced length of ICU and hospital stay with the use of Plasma-Lyte® 148.
Given the clinical uncertainty and substantial variability in practice. there is a scientific, clinical and health economic imperative to conduct a high-fidelity study to provide definitive evidence to inform clinicians regarding the choice of resuscitation fluids for patients with DKA. BEST-DKA will address this critical knowledge gap.
BEST-DKA is a multi-centre, blinded, cluster-crossover trial conducted in 20 Australian hospitals, consisting of two 12-month intervention periods with a one-month inter-period gap.
Each hospital is a single cluster, with all patients admitted with DKA to that hospital's ED during the intervention periods will potentially be eligible for inclusion in the trial. After the first 12-month intervention period during which recruited patients will receive either Plasma-Lyte® 148 or 0.9% saline, there will be a one-month inter-period gap during which patients will not be recruited into the trial. Following this each critical care area will change to using the fluid to which they were not assigned for the first period (Figure 4). All included patients will receive blinded fluids (Plasma-Lyte® 148 or 0.9% saline) as part of their DKA therapy depending on the fluid assigned to the site for the relevant intervention period.
Both study fluids are manufactured by Baxter Healthcare Pty Ltd (Old Toongabbie, NSW) and will be labelled, packed and distributed by the company directly to the study sites in periodic shipments. Study fluid will be coded and labelled in compliance with applicable regulations, and in a manner that protects the blinding.
All clinicians involved in the prescription of blinded study treatment must read Product Information for both Plasma-Lyte® 148 and 0.9% saline which provide detailed information about the composition, indications, side effects, suggested dosage and contraindications of the study treatments.
The volume and rate of blinded study fluid administered will be guided by the standard clinical endpoints determined by the treating clinician. Study treatments will be started following study enrolment and continue until discharge from a critical care area or for a maximum of 72 hrs, whichever is earlier. If patients are re-admitted to the critical care area within 72 hours with a relapse of ketoacidosis, the clinician may use open label fluids for the managements of ketoacidosis. within 72 hours they will continue to receive blinded treatment fluid. Glucose containing solutions can be added in as required for blood glucose or ketosis management. The use of bicarbonate therapy and the need for potassium, phosphate and magnesium supplementation will be at the discretion of the treating clinician and data on its use will be collected.
The primary outcome will be evaluated at day-28 and patients contacted via telephone.
End-user/consumer representatives have been involved in all components of the research program including protocol development, choice of primary outcome, funding applications, and membership of the management committee. End-user/consumer representatives will continue to be involved in the conduct of the study and play a key role in the dissemination of results. Currently, membership of the study management committee includes the President of the advocacy group, Diabetes Australia; Director of Australian Centre for Accelerating Diabetes Innovations (ACADI); and a consumer who lives with diabetes.
This study aligns with the Medical Research Future Fund (Australia Government grant) funded ACADI objective to address the acute complications of diabetes including management of DKA.
The study has been endorsed by the Australasian College for Emergency Medicine (ACEM) and a letter of support from for the study from Diabetes Australia.
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
-
-
New South Wales
-
Blacktown、New South Wales、オーストラリア、2148
- Blacktown Hospital
-
Campbelltown、New South Wales、オーストラリア、2560
- Campbelltown Hospital
-
Dubbo、New South Wales、オーストラリア、2830
- Dubbo Base Hospital
-
Kogarah、New South Wales、オーストラリア、2217
- St George Hospital
-
Metford、New South Wales、オーストラリア、2323
- Maitland Hospital
-
Orange、New South Wales、オーストラリア、2800
- Orange Hospital
-
St Leonards、New South Wales、オーストラリア、2065
- Royal North Shore Hospital
-
Westmead、New South Wales、オーストラリア、2145
- Westmead Hospital
-
-
Queensland
-
Birtinya、Queensland、オーストラリア、4575
- Sunshine Coast University Hospital
-
Caboolture、Queensland、オーストラリア
- Caboolture Hospital
-
Coopers Plains、Queensland、オーストラリア、4108
- Queen Elizabeth II Jubilee Hospital
-
Redcliffe、Queensland、オーストラリア、4020
- Redcliffe Hospital
-
Rockhampton、Queensland、オーストラリア、4700
- Rockhampton Hospital
-
Southport、Queensland、オーストラリア、4215
- Gold Coast University Hospital
-
-
South Australia
-
Elizabeth Vale、South Australia、オーストラリア、5112
- Lyell McEwin Hospital
-
Woodville South、South Australia、オーストラリア、5011
- The Queen Elizabeth Hospital
-
-
Victoria
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Ballarat、Victoria、オーストラリア、3350
- Ballarat Base Hospital
-
Berwick、Victoria、オーストラリア、3806
- Monash Health-Casey Hospital
-
Dandenong、Victoria、オーストラリア、3175
- Dandenong Hospital
-
Frankston、Victoria、オーストラリア、3199
- Frankston Hospital - Peninsula Health
-
Traralgon、Victoria、オーストラリア、3844
- Latrobe Regional Hospital
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Patients in the ED with a primary diagnosis of moderate to severe DKA for whom both saline and Plasma-Lyte® 148 are considered appropriate fluids
- Blood glucose level > 14mmol/L
- pH < 7.25
- Serum bicarbonate <15 mmol/L
- Elevated anion gap > 12mEq/L
- Ketones positive on finger prick measurements
- In the judgement of the treating clinician critical care area admission is required
Exclusion Criteria:
- Age less than 18 years
- Patients who have received more than 2000ml of non study fluid prior to study enrolment
- Serum Na > 155 or <120 mmol/L
- Contraindication to either study fluid e.g. previous allergic reaction to Plasma-Lyte® 148
- Patients with hyperosmotic hyperglycaemic non-ketotic syndrome
- Other clinical conditions that preclude large volumes of fluid resuscitation
- Previous inclusion in BEST-DKA trial
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：クロスオーバー割り当て
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：Plasma-Lyte® 148
Plasma-Lyte® 148 fluid 1L given intravenously for fluid replacement |
Plasma-Lyte® 148 intravenous fluid for resuscitation in patients with keto-acidosis
他の名前：
|
|
アクティブコンパレータ：0.9% sodium chloride
Normal saline fluid 1L given intravenously for fluid replacement |
0.9% sodium chloride intravenous fluid for resuscitation in patients with keto-acidosis
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Hospital free days (HFD) up to day-28 after study enrolment
時間枠：from time of enrolment to 28 days
|
Number of hospital free days from time of hospital discharge |
from time of enrolment to 28 days
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
ICU free days up to 28 days after study enrolment
時間枠：28 days after enrolment
|
Number of ICU free days from time of ICU discharge |
28 days after enrolment
|
|
ICU and hospital readmissions up to 28 days after study enrolment
時間枠：28 days after enrolment
|
Number of days free from ICU and hospital from time of hospital discharge |
28 days after enrolment
|
|
Acute kidney injury assessed by comparing serum creatinine using Kidney Disease: Improving Global Outcomes (KDIGO) criteria
時間枠：28 days after enrolment
|
injury assessed by comparing change in serum creatinine using Kidney Disease: Improving Global Outcomes (KDIGO) criteria |
28 days after enrolment
|
|
Episodes of post-study enrolment decrease in Glasgow Coma Scale (GCS) by more than 2 in the first 24 hours
時間枠：first 24 hours from enrolment
|
decrease in Glasgow Coma Score by more than 2 points |
first 24 hours from enrolment
|
|
Time to resolution of ketosis
時間枠：from time of enrolment to day 28
|
resolution of acidosis |
from time of enrolment to day 28
|
|
Cumulative insulin dosage in the first 48 hours
時間枠：first 48 hours from time of enrolment
|
Total amount of insulin given to the patient from enrolment to 48 hours |
first 48 hours from time of enrolment
|
|
Duration of IV insulin infusion
時間枠：from time of enrolment to day 28
|
Total amount of IV insulin given to the patient from time of enrolment to day 28 |
from time of enrolment to day 28
|
|
Cumulative potassium replacement
時間枠：from time of enrolment to day 28
|
Total amount of potassium given to the patient from time of enrolment to day 28 |
from time of enrolment to day 28
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Cost-effectiveness
時間枠：from time of enrolment to day 28
|
Calculation of the incremental cost-effectiveness ratios |
from time of enrolment to day 28
|
協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- TGI CCP-2378-352
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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