The Intensive Care Platform Trial (INCEPT)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 10,000
- 试验地点
- 33
- 主要终点
- Days alive and out of hospital at day 30 (Thromboprophylaxis domain)
研究概览
简要总结
Among critically ill patients, many die, and many of the survivors and their family members struggle for years with reduced quality of life. Critically ill patients are treated in intensive care units (ICUs). Here, they receive life support, e.g., mechanical ventilation and advanced support of the circulation (heart and blood vessels) and kidneys. In addition, ICU patients receive many other treatments. It is, however, uncertain if all the treatments provide value for the patients. The desirable effects of many treatments are uncertain, and some may be wasteful or even harmful.
Clinical trials are necessary to validly assess the desirable and undesirable effects of different treatments. However, conventional clinical trials have limitations:
- They typically only assess a single question related to a single comparison of treatments at a time.
- They are often not very flexible, including with regards to the number of participants needed, and this increases the risk that a trial will end up as inconclusive.
- There is no or limited re-use or sharing of infrastructure across trials, leading to duplicate work and resource use.
- Trial participants do usually not benefit from the obtained knowledge before the trial concludes.
- Involvement of patients, family members, and other stakeholders is typically limited, which may decrease the relevance of the questions addressed.
With the Intensive Care Platform Trial (INCEPT), we aim to tackle these challenges by establishing a flexible platform trial that continuously learns from the obtained results. The platform trial may run forever with simultaneous and continuous assessment of many treatments. INCEPT will continuously learn from the accrued data and use these to improve the treatment of both participating and future patients. With INCEPT, we are also building a framework for thorough and extensive involvement of key stakeholders, including patients and family members. INCEPT will improve the way clinical trials are done and increase the probabilities that treatments are improved. This will:
- Directly improve outcomes for ICU patients.
- Relieve a strained healthcare system by discarding inefficient or harmful treatments.
- Ensure that new treatments are beneficial or cost-effective before implementation.
- Lower the costs and burdens of assessing more treatments in the critically ill.
详细描述
Background:
Randomised clinical trials (RCTs) are the gold standard for evaluating intervention effects, however, conventional RCTs are bureaucratic, costly, inflexible, and often inconclusive. Adaptive platform trials are increasingly used as they can reduce barriers and are more flexible, and thus come with a higher probability of obtaining conclusive results faster at lower costs.
Objectives:
The Intensive Care Platform Trial (INCEPT) will be used to assess the effects of interventions used in adults acutely admitted to the intensive care unit (ICU).
Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Domains may be open-label or blinded (masked). Outcome assessment of health-related quality of life and cognitive function will always be blinded.
入排标准
- 年龄范围
- 18 Years 至 65+ years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The general eligibility criteria below apply to INCEPT as a whole and thus to all domains. Domains may impose domain-specific eligibility criteria that restrict the population eligible for that domain further, but domains are not allowed to broaden the general eligibility criteria. Domain-specific eligibility criteria always apply to all arms in a domain.
- •PLATFORM INCLUSION CRITERIA:
- •Adult patient (≥18 years old) acutely admitted to the ICU. This includes ICU admissions after emergency surgery, unplanned ICU admissions after elective surgery, and prolonged ICU admissions due to complications after elective surgery (i.e., admissions occurring or being prolonged due to an unexpected, worsened condition, but excluding planned ICU admissions after elective surgery without clinical deterioration).
- •Eligible for at least one active domain.
排除标准
- •Informed consent following inclusion expected to be unobtainable (e.g., known previous objections to participation).
- •Patient is under coercive measures (e.g., ongoing involuntary hospital stay or under the jurisdiction of correctional authorities).
- •Patients who have previously been included in INCEPT may only be included again during new ICU admissions but may only be randomised to domains in which they have not previously been randomised.
- •DOMAIN-SPECIFIC ELIGIBLE CRITERIA:
- •Each domain may have additional eligibility criteria. Refer to the study website for more information (www.incept.dk).
研究组 & 干预措施
Albumin
Use of albumin in ICU during circulatory failure in addition to crystalloids (resuscitation) and for substitution in case of suspected or overt albumin loss or plasma albumin levels ≤25 g/L
干预措施: Albumin (Drug)
No albumin use
No albumin is to be used in ICU unless specific events occur
干预措施: No albumin use (Other)
Low-molecular-weight heparin for thromboprophylaxis in weight-adjusted dose
Use of low-molecular-weight heparin for thromboprophylaxis in weight-adjusted dose during ICU stay
干预措施: LMWH in weight-adjusted dose (Drug)
Low-molecular-weight heparin for thromboprophylaxis in fixed low dose
Use of low-molecular-weight heparin for thromboprophylaxis in fixed low dose during ICU stay
干预措施: LMWH in fixed low dose (Drug)
Low-molecular-weight heparin for thromboprophylaxis in fixed intermediate dose
Use of low-molecular-weight heparin for thromboprophylaxis in fixed intermediate dose during ICU stay
干预措施: LMWH in fixed intermediate dose (Drug)
结局指标
主要结局
Days alive and out of hospital at day 30 (Thromboprophylaxis domain)
时间窗: From randomisation to 30 days after randomisation.
Days alive and out of hospital. Rehabilitation facilities and nursing homes do not count as hospitals. Integer 0-29.
One of the INCEPT core outcomes (varying between domains)
时间窗: From randomisation to 30-180 days after randomisation.
Each domain in INCEPT will use one of the core outcomes; 1. All-cause 30-day mortality. 2. All-cause 90-day mortality. 3. All-cause 180-day mortality. 4. Days alive without life support at day 30. 5. Days alive without life support at day 90. 6. Days alive out of hospital at day 30. 7. Days alive out of hospital at day 90. 8. Days free of delirium at day 30. 9. EQ VAS (Health-Related Quality of Life) at day 180. 10. EQ-5D-5L index values (Health-related quality of life) at day 180. 11. Cognitive function at day 180 (all described under "secondary outcomes").
Days alive without life support at day 30 (Albumin domain)
时间窗: From randomisation to 30 days after randomisation.
Days alive without the use of life support, with life support defined as invasive mechanical ventilation (≥1 hour of ventilation through a cuffed tube), continuous (i.e., ≥1 hour) use of vasopressors/inotropes, use of renal replacement therapy (including any form of in-hospital renal replacement therapy \[e.g., haemodialysis, haemofiltration, or haemodiafiltration\], continuously or intermittently, and including days in between intermittent renal replacement therapy; pauses between renal replacement therapy of up to three days will be considered as days receiving intermittent renal replacement therapy) at hospitals. Integer (0-30 overall; 0-29 in domains with life support at baseline as an eligibility criterion).
次要结局
- All-cause 90-day mortality(90 days after randomisation.)
- Days alive out of hospital at day 30(From randomisation to 30 days after randomisation.)
- Cognitive function at day 180(180 days after randomisation (+/- 14 days).)
- All-cause 30-day mortality(30 days after randomisation.)
- All-cause 180-day mortality(180 days after randomisation.)
- Days alive without life support at day 30(From randomisation to 30 days after randomisation.)
- Days alive without life support at day 90(From randomisation to 90 days after randomisation.)
- Days alive out of hospital at day 90(From randomisation to 90 days after randomisation.)
- Days free of delirium at day 30(From randomisation to 30 days after randomisation.)
- EQ VAS (Health-Related Quality of Life) at day 180(180 days after randomisation (+/- 14 days).)
- EQ-5D-5L index values (Health-Related Quality of Life) at day 180(180 days after randomisation (+/- 14 days).)
- Thromboprophylaxis domain specific secondary outcomes(30 days (matching the primary and guiding outcome) and 90 days (matching the maximum intervention period).)
研究者
Anders Perner
Professor, senior staff specialist
Rigshospitalet, Denmark