NCT Number: NCT06667999
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.
Interested in participating?
Request Info18 year and older
All sexes
Interventional
Phase 4
Anaesthesia, Hospital Sønderjylland, Aabenraa, Denmark
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:
INCEPT is an investigator-initiated, pragmatic, randomised, embedded, multifactorial, international, adaptive platform trial. INCEPT uses adaptive stopping and arm-dropping rules, as well as fixed and response-adaptive randomisation. Specific domains may be either open label or blinded.
Domains and interventions:
Comparable groups of interventions will be nested in domains, which have conceptual similarities with stand-alone randomised trials. Domains will continuously be added to INCEPT and conducted following domain-specific appendices to the core protocol.
Inclusion and exclusion criteria:
Adults acutely admitted to the ICU will be screened if they are eligible for at least one active domain. The only platform-level exclusion criteria are 1) informed consent after inclusion expected to be unobtainable and 2) patients admitted under coercive measures. Additional inclusion and exclusion criteria will be domain-specific.
Stakeholder involvement:
Stakeholder involvement is central in INCEPT and ensured through a central advisory board comprising various key stakeholders, and consultations with national and international research panels consisting of ICU survivors, family members, clinicians, and researchers. Stakeholders will be involved in the development of the overall platform trial and specific domains with pre-specified minimum requirements for involvement.
Outcomes:
Each domain will use one of the core outcomes (defined elsewhere in the registration) as the primary outcome and the guiding outcome driving all adaptations.
Statistical methods Primary analyses will generally be conducted in the intention-to-treat population of each domain. INCEPT primarily uses Bayesian statistical methods with neutral priors conveying either minimal information or some scepticism, although specific domains may use conventional, frequentist statistical methods. Outcomes will generally be analysed using logistic and linear regression models adjusted for pre-specified anticipated prognostic baseline characteristics, followed by calculation of sample-average estimates and intervention effects using G-computation. Results will be presented for each intervention and comparisons presented on both the absolute (risk differences and mean differences) and relative (risk ratios and ratios of means) scales with 95% credible intervals and probabilities of superiority. INCEPT will generally use constant, symmetric stopping rules for superiority/inferiority based on the guiding outcome; domains may use stopping rules for practical equivalence or futility based on the posterior distribution of the guiding outcome on the absolute scale. All stopping rules will be binding. Response-adaptive randomisation, either with or without restrictions, may be used based on the posterior distribution for the guiding outcome. Missing data will be multiply imputed. Additional secondary analyses (e.g., per-protocol analyses), sensitivity analyses, and analyses of heterogeneity in intervention effects according to pre-defined baseline characteristics may be specified for each domain and undertaken once a domain has stopped. Domains will be designed and evaluated using statistical simulation.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
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:
PLATFORM EXCLUSION CRITERIA:
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).
Albumin should be used for the following indications: 1. During circulatory failure in addition to crystalloids (resuscitation). 2. For substitution in case of: suspected or overt albumin loss OR P-albumin levels below or equal to 25 g/L. Decisions around timing, volume, and concentration of albumin, and its use for other indications, are at the clinician's discretion. P-albumin should be measured according to local practice.
Albumin should not be used. In case of the following special circumstances, albumin may be considered: 1. Large ascites drainage (i.e., equal to or more than 1 L tapped) 2. Spontaneous bacterial peritonitis 3. Hepatorenal syndrome.
Patients with indication for thromboprophylaxis receive low-molecular-weight heparin (LMWH) in a weight-adjusted dose during their ICU stay. The treating clinician may decide to adjust or withhold one or more doses in case of acute and/or chronic kidney injury, renal replacement therapy, thrombocytopenia, invasive procedures, use of thrombolysis, and active (major) bleeding.
Patients with indication for thromboprophylaxis receive low-molecular-weight heparin (LMWH) in a fixed low dose during their ICU stay. The treating clinician may decide to adjust or withhold one or more doses in case of acute and/or chronic kidney injury, renal replacement therapy, thrombocytopenia, invasive procedures, use of thrombolysis, and active (major) bleeding.
Patients with indication for thromboprophylaxis receive low-molecular-weight heparin (LMWH) in a fixed intermediate dose during their ICU stay. The treating clinician may decide to adjust or withhold one or more doses in case of acute and/or chronic kidney injury, renal replacement therapy, thrombocytopenia, invasive procedures, use of thrombolysis, and active (major) bleeding.
Time frame: 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").
Time frame: 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).
Time frame: 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.
Time frame: 30 days after randomisation.
All-cause, fixed-time mortality. Binary.
Time frame: 90 days after randomisation.
All-cause, fixed-time mortality. Binary.
Time frame: 180 days after randomisation.
All-cause, fixed-time mortality. Binary.
Time frame: 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).
Time frame: From randomisation to 90 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 (0-90 overall; 0-89 in domains with life support at baseline as an eligibility criterion).
Time frame: 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.
Time frame: From randomisation to 90 days after randomisation.
Days alive and out of hospital. Rehabilitation facilities and nursing homes do not count as hospitals. Integer 0-89.
Time frame: From randomisation to 30 days after randomisation.
Days free of delirium. Days are not considered free of delirium in case of any of the following: a) any registered positive delirium score with a validated screening tool (Confusion Assessment Method for the Intensive Care Unit [CAM-ICU], CAM-ICU-7 or Intensive Care Delirium Screening Checklist [ICDSC]) b) new treatment with antipsychotics (any administration of haloperidol, olanzapine, or quetiapine in participants not receiving either of these at the time of index hospital admission) c) delirium status not evaluable due to mortality or registered coma. Integer (0-30 overall; 0-29 in domains with delirium at baseline as an eligibility criterion).
Time frame: 180 days after randomisation (+/- 14 days).
EQ-5D-5L instrument with responses across five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with five response levels each. Used with a value set to calculate index values anchored at 1 (perfect health) and 0 (a health state considered as bad as being dead) with index values below 0 representing health states worse than death. Preferably completed by participants, but completed by proxies if participants are unable to answer (using the proxy-participant perspective, i.e., the proxy will answer from the participant's perspective as the limited, indirect data available indicates that this perspective may better correspond to the participant's own response, if available). Decimal number (minimum values depend on value sets used, e.g., -0.758 with the Danish value set; maximum value: 1.000).
Time frame: 180 days after randomisation (+/- 14 days).
A visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state), part of the EQ-5D-5L instrument
Time frame: 180 days after randomisation (+/- 14 days).
Montreal Cognitive Assessment test 5-minute version, v2.1 ("Mini MoCA"), ranging from 0 points (worst) to 15 points (best).
Time frame: 30 days (matching the primary and guiding outcome) and 90 days (matching the maximum intervention period).
The number of participants with one or more domain-specific secondary outcomes, i.e., venous thromboembolism or major bleeding as specified in the domain-specific appendix.
Time frame: 30 days (matching the primary and guiding outcome) and 90 days (matching the maximum intervention period.
Albumin domain: The number of participants with one or more safety outcomes, i.e. severe anaphylatic reaction or major bleedings as specified in the domain specific appendix.
Time frame: 30 days (matching the primary and guiding outcome) and 90 days (matching the maximum intervention period).
The number of participants with one or more safety outcomes, i.e. severe anaphylactic reaction to LMWH or heparin-induced thrombocytopenia as specified in the domain specific appendix.
Contact information is provided by the study sponsor or research team.
Anders Perner, Professor
CONTACT
Morten H Moeller, Professor
CONTACT
Anders Perner
Other
The Intensive Care Platform Trial (INCEPT)
Acronym: INCEPT
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
Published trials that share one or more normalized conditions with this study.
NCT07345169
Critical Illness, Critical Illness Requiring Intensive Care - Acute Brain Injury
Paris, France
View Trial DetailsNCT07107685
Infections, Inflammation
Paris, France
View Trial DetailsNCT06121050
Intensive Care Patients
Annonay, France
View Trial DetailsNCT06770751
Delirium in the Intensive Care Unit, Family
Istanbul, Turkey (Türkiye)
View Trial Details