Ethics approval and consent to participate
The trial was approved by the Ethics Committee for Multi-Centric Clinical Trials University Hospital Brno on January 28, 2021 Identifier: 11/21-MEK.
This trial will be conducted following the applicable legislation and requirements for good clinical practice according to ICH E6(R2). Compliance with this standard provides public assurance that the rights, safety and well-being of trial participants are protected and that the clinical trial data are credible. All potential amendments will be submitted to the relevant Ethics committee and Regulatory authority for approval.
Informed consent procedure
The investigator assesses the patient’s ability to decide, and the extent of potential consciousness impairment based on Glasgow Coma Score and other appropriate clinical measures (at the discretion of the trial centre).
Fully conscious and oriented patients (GCS 15)
Patient with decision-making capacity will go through the standard procedure (informative interview with the investigator, written information for the patient, the possibility to ask questions, and adequate time to discuss with family and decide). If the patient wishes to participate, he/she will provide written prospective informed consent.
Patients with limited ability to decide (GCS 13 or 14)
Some patients may be limited in their decisional capacity due to their acute health status and/or medication. Generally, if a patient understands simplified information and can communicate verbally, the simplified procedure of obtaining informed consent will be applied. The shortened (one-page) information sheet and consent form for signature will be used.
As soon as the patient regains full decisional capacity, he/she will be approached to provide consent for continuation of his/her participation in the trial. Patients will be informed about the option to withdraw from the trial. Patients who decide to terminate their involvement can permit the sponsor to use the data collected, or they can ask for deletion of all data collected. Both options will be presented to them.
If the patient does not regain decisional capacity, the initial consent will remain valid.
Patients lacking the capacity to decide (GCS 12 or less)
It is expected that a significant proportion of screened patients will lack capacity to provide informed consent due to severely altered consciousness, severe respiratory distress, or sedation necessary to facilitate mechanical ventilation. In this situation, the deferred consent policy will be applied. Such a patient will be enrolled after an independent physician witnesses (in writing) that the patient cannot give his/her consent and fulfils eligibility criteria.
A patient's close person (spouse/partner, close relative, caregiver) will be informed about the patient's enrolment and the nature of the study. If possible, and compliant with the epidemiological restrictions by the government, the patient's close person will meet the investigator for an informative interview, to obtain the information leaflet, and to sign a confirmation that he/she was informed about the patient's participation in the trial.
As soon as the patient regains decisional capacity, he/she will be approached to provide consent for continuation of his/her participation in the trial. Patients will be informed about the option to withdraw from the trial. Patients who decide to terminate their involvement can permit the sponsor to use data collected, or can ask for deletion of all data collected to date. Both options will be presented to them.
If the patient does not regain decisional capacity, the initial consent by an independent physician will remain valid.
Beside patients with diminished decision capacity, other specifically vulnerable participants (children, pregnant women, prisoners, refugees, institutionalized patients, patients with severe mental illnesses, etc.) will not be enrolled in this clinical trial.
Consent for publication
Availability of data and materials
The sponsor, the trial site and study staff will handle the subject's personal and trial data according to the effective legislation regarding data protection. Collected data will be shared with other ongoing clinical trials on the same topic for individual patient data (IPD) meta-analysis or shared upon relevant requests. A de-identified participant-level dataset will be made available 6 months after publication of the results of the study at www.mendeley.com
Investigators declare no financial or non-financial competing interest regarding the focus of this trial.
REMED is an investigator-initiated clinical trial. Funding will be granted from the project research infrastructure Czech Clinical Research Infrastructure Network CZECRIN (LM 2018128), University Hospital Brno and Endowment fund Donatio Intensivistam (VAT No 0907206). Trial funders have no role in the study design, collection, analysis and interpretation of data nor in writing the manuscript.
JM and JS conceived the study and wrote the original protocol draft. JM led the protocol and proposal development, selected and contracted sites. RG selected and contracted sites. FD, MB, JZ, MK, JK, MS contributed to study design and to development of the proposal. JMac, JH, TV, OK, TG, PN reviewed the original draft. RD, JK, JV are clinical research specialists. AS is the trial statistician and analyst. All authors read and approved the final manuscript.
The authors thank Dita Budňáková, Ĺubica Horváthová, Karolína Grodová, Jarmila Havlová and Iva Knápková for the help and wonderfull assistance during preparation of the protocol and Lenka Dobrovolná for administrative assistance.
REMED Study Group:
University Hospital Brno: Helena Antoni, Petr Suk, Tomáš Korbička, Jan Hudec; University Hospital Královské Vinohrady: Michal Fric, Václav Zvoníček, Tomáš Tencer, Martin Kolář, Petr Kafka; General University Hospital in Prague: Michal Otáhal, Jan Rulíšek, Marek Flaksa, Eva Svobodová; University Hospital Ostrava: Peter Sklienka, Filip Burša, Marcela Káňová, Jan Varady, Filip Haiduk; St. Anne’s University Hospital: Vladimír Šrámek, Pavel Suk, Marek Fencl, Ivan Čundrle, Pavel Štětka, Marek Lukeš, Miloš Chobola; University Hospital Motol: Jan Beroušek, Zuzana Přikrylová, Jiří Bureš, Jaromír Vajter, Vlasta Vlasáková, Michal Garaj; University Hospital Olomouc: Lenka Doubravská; University Hospital Plzeň: Jiří Pouska, Jakub Kletečka; Tomáš Baťa Regional Hospital: Tomáš Graus, Tereza Šobáňová, Radovan Turek; Military University Hospital Praha: Tomáš Tyll, Aleš Rára;
Supported by the national budget through MEYS, RI CZECRIN (LM2018128) and from ERDF Project CZECRIN_4 PATIENTS (CZ.02.1.01/0.0/0.0/16_013/0001826) and by MH CZ - DRO (FNBr, 65269705) and Endowment fund Donatio Intensivistam (VAT No 0907206).