E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute hypoxaemic respiratory failure in patients admitted to the intensive care unit |
|
E.1.1.1 | Medical condition in easily understood language |
Patients with acute pulmonary failure and inadequate oxygenation of the blood, admitted to an intensive care unit |
Tehohoitopotilaita, joilla akuutti veren matalaa happipitoisuutta aiheuttava hengitysvajaus |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001053 |
E.1.2 | Term | Acute respiratory failure |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022519 |
E.1.2 | Term | Intensive care |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the benefits and harms of two targets of partial pressure of oxygen in arterial blood in guiding the oxygen administration in acutely ill adults with hypoxaemic respiratory failure at ICU admission. |
Tutkimuksessa selvitetään kahden hapen annostelussa käytettävän valtimoveren happipitoisuustavoitteen hyötyjä ja haittoja tehohoidossa olevilla aikuispotilailla, joilla on akuutti hypoksemiaa aiheuttava hengitysvajaus. |
|
E.2.2 | Secondary objectives of the trial |
To asses health economic implications of two targets of partial pressure of oxygen in arterial blood in guiding the oxygen administration in acutely ill adults with hypoxaemic respiratory failure at ICU admission. Conducted through a health economic analysis at one year follow-up of the last enrolled patient. |
Arvioidaan onko hapen annostelua ohjaavilla valtimoveren happipitoisuustavoitteilla terveystaloudellisia vaikutuksia tehohoidossa olevilla aikuispotilailla, joilla on akuutti hypoksemiaa aiheuttava hengitysvajaus |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Acutely admitted to the intensive care unit AND
- Aged ≥ 18 years AND
- Receive supplemental oxygen with a flow of at least 10 L per minute in an open system or at least an fraction of inspired oxygen of 0.50 in a closed system, including invasive ventilation, non-invasive ventilation or continuous positive airway pressure AND
- Are expected to receive oxygen administration for at least 24 hours in the ICU AND
- Have an arterial line in place |
- päivystyksellinen tehohoidon tarve JA
- ≥ 18 vuotias JA
- tarve sisäänhengityksen lisähapelle vähintään 10 litraa/min avoimessa systeemissä tai happifraktiolla 0.5 suljetussa systeemissä (noninvasiivinen tai invasiivinen hengityslaitehoito, myös jatkuva positiivinen ilmatiepaine CPAP) JA
- lisähapen annon tarpeen tehohoidossa arvioidaan jatkuvan vähintään 24 tuntia JA
- valtimokanyyli asetettu |
|
E.4 | Principal exclusion criteria |
- Cannot be randomised within twelve hours after present ICU admission
- Chronic mechanical ventilation for any reason
- Use of home oxygen
- Previous treatment with bleomycin
- Organ transplant during current hospital admission
- Withdrawal from active therapy or brain death deemed imminent
- Fertile woman with positive urine human gonadotropin (hCG) or
plasma-hCG
- Carbon monoxide poisoning
- Cyanide poisoning
- Methaemoglobinaemia
- Paraquat poisoning
- Any condition expected to involve the use of hyperbaric oxygen (HBO)
- Sickle cell disease
- Consent not obtainable according to national regulations
- Previously randomised into the HOT-ICU trial |
- randomisaatio ei mahdollinen 12 tunnin sisällä teho-osastolle ottamisesta
- pysyvä hengityslaitehoito
- pysyvä lisähapen tarve
- aikaisempi hoito bleomysiinillä
- elinsiirtoleikkaus nykyisellä sairaalahoitojaksolla
- aktiivihoidosta luovuttu tai aivokuolema todennäköinen
- raskaus
- häkämyrkytys
- syanidimyrkytys
- methemoglobinemia
- parakvattimyrkytys
- ylipainehappihoitoa vaativa tila
- sirppisoluanemia
- ei tietoista suostumusta
- randomoitu jo aiemmin HOT-ICU-tutkimukseen
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
90 days post-randomisation |
90 päivää randomisaation jälkeen |
|
E.5.2 | Secondary end point(s) |
- Number of patients with one or more SAEs in the ICU after randomisation; SAEs are defined as new episode of shock and new episodes of ischemic events including myocardial or intestinal ischaemia or ischemic stroke in the 90-day period
- Days alive without the use of respiratory support, renal replacement therapy or circulatory support in the 90-day period
- Days alive out of the hospital in the 90-day period
- Mortality 1-year after randomisation
- Health related quality of life (Euroqual, EQ-5D-5L) 1-year after randomisation.
- Cognitive function 1-year after randomisation as assessed using RBANS score in selected sites
- A health economic analysis based on the result of the trial and specified (cost-effectiveness versus cost-minimisation analyses) |
- potilaiden määrä, joilla vähintään yksi SAE; SAE:n määritelmänä 1) uusi shokki 2) uusi iskeeminen tapahtuma (sydänlihasiskemia, suolistoiskemia tai iskeeminen aivotapahtuma 90 päivän aikana)
- elossaolopäivät ilman hengityslaitehoitoa, munuaiskorvaushoitoa tai verenkierron tukihoitoja 90 päivän aikana
- elossaolopäivät sairaalan ulkopuolella 90 päivän aikana
- kuolleisuus vuoden kuluttua randomisaatiosta
- terveyteen littyvä elämänlaatu (Euroqual, EQ-5D-5L) vuoden kuluttua randomisaatiosta
- kognitiivinen toiminta vuoden kuluttua randomisaatiosta RBANS asteikolla arvioituna (osa keskuksista)
- terveystalousanalyysi, joka pohjautuu tutkimustulokseen ja määriteltyihin analyyseihin (kustannustehokkuus ja kustannusminimisaatio) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Hapen eri annostelu. Vertailuna korkeampi happeutumistavoite. |
Different dosage of oxygen. The comparator is the highest oxygenation target. |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Denmark |
Finland |
Iceland |
Netherlands |
Norway |
Sweden |
Switzerland |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Trial allocation is planned to end when 2 x 1464 (2928) patients have been randomised (April 2019) and 90-days follow-up has been completed (July 2019).
The patients will be contacted one year after randomisation (last patient contacted April 2020) to conduct follow-up on health related quality of life and cognitive function (selected sites). |
Tutkimuksen sisäänoton on suunniteltu päättyvän, kun2 x 1464 (2928) potilasta on randomoitu (huhtikuu 2019) ja 90-päivän seuranta on päättynyt (heinäkuu 2019).
Potilaisiin otetaan yhteyttä vuoden kuluttua randomisaatiosta (viimeinen yhteydenotto huhtikuussa 2020) ja selvitetään terveyteen liittyvä elämänlaatu ja kognitiivinen toimintakyky (tietyissä keskuksissa) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |