The Intensive Care Platform Trial

Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorAnders Perner

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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).

Trial design

Design model

Parallel

Treatments tested in this trial

  • Albumin

    Drug

    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.

  • No albumin use

    Other intervention

    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.

  • LMWH in weight-adjusted dose

    Drug

    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.

  • LMWH in fixed low dose

    Drug

    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.

  • LMWH in fixed intermediate dose

    Drug

    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.

Treatment groups

10,000 Participants
are divided into 5 treatment groups
Group A: AlbuminExperimental treatment 1 intervention
Group B: No albumin useOther 1 intervention
Group C: Low-molecular-weight heparin for thromboprophylaxis in weight-adjusted doseExperimental treatment 1 intervention
Group D: Low-molecular-weight heparin for thromboprophylaxis in fixed low doseActive comparator 1 intervention
Group E: Low-molecular-weight heparin for thromboprophylaxis in fixed intermediate doseActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

One of the INCEPT core outcomes (varying between domains)

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 30-180 days after randomisation.
2

Days alive without life support at day 30 (Albumin domain)

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.
3

Days alive and out of hospital at day 30 (Thromboprophylaxis domain)

Days alive and out of hospital. Rehabilitation facilities and nursing homes do not count as hospitals. Integer 0-29.

Time frame
From randomisation to 30 days after randomisation.

Secondary outcomes

1

All-cause 30-day mortality

All-cause, fixed-time mortality. Binary.

Time frame
30 days after randomisation.
2

All-cause 90-day mortality

All-cause, fixed-time mortality. Binary.

Time frame
90 days after randomisation.
3

All-cause 180-day mortality

All-cause, fixed-time mortality. Binary.

Time frame
180 days after randomisation.
4

Days alive without life support at day 30

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.

Other outcomes

1

Albumin domain-specific safety outcomes

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.
2

Thromboprophylaxis domain-specific safety outcomes

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.

Time frame
30 days (matching the primary and guiding outcome) and 90 days (matching the maximum intervention period).

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Anders Perner

Lead sponsor

Copenhagen University Hospital, Rigshospitalet

Sponsor institution

Copenhagen University Hospital, Rigshospitalet

Collaborator

Bispebjerg Hospital

Collaborator

Herlev Hospital

Collaborator

Hillerod Hospital, Denmark

Collaborator

Kolding Sygehus

Collaborator

Zealand University Hospital

Collaborator

Slagelse Hospital

Collaborator

Viborg Regional Hospital

Collaborator

Aalborg University Hospital

Collaborator

Aarhus University Hospital

Collaborator

Gødstrup Hospital

Collaborator

Copenhagen University Hospital, Hvidovre

Collaborator

Odense University Hospital

Collaborator

Randers Regional Hospital

Collaborator

University of Copenhagen

Collaborator

North Denmark Region

Collaborator

Region Capital Denmark

Collaborator

Region Zealand

Collaborator

University Medical Center Groningen

Collaborator

Steno Diabetes Center Copenhagen

Collaborator

Karolinska Institutet

Collaborator

Oslo University Hospital

Collaborator

University Hospital, Basel, Switzerland

Collaborator

Tampere University

Collaborator

Collaboration of Research in Intensive Care

Collaborator

Danish Intensive Care Database

Collaborator

The National University Hospital of Iceland

Collaborator