Intravenous Lidocaine for Hepatectomy (ILHEP)
Effect of Perioperative Intravenous Lidocaine on Postoperative Opioid Related-side Effects After Open HEPatectomy: a Multicentre Prospective Randomized Controlled Study
Liver resection is increasingly performed for hepatic tumors, mainly primary liver cancers and resectable metastases, but also for some benign lesions. Postoperative pain is often significant, regardless of the surgical technique, making effective pain control essential to promote early mobilization and reduce complications.
Current standard care relies on multimodal analgesia, combining several drugs administered during surgery, with morphine administered as rescue therapy when required. Morphine is associated with side effects such as nausea, vomiting, ileus, hypoxemia, opioid-induced hyperalgesia, and transient cognitive impairment. Therefore, there is a need to optimize pain management while reducing opioid consumption and related adverse effects.
Intravenous (IV) lidocaine has well-documented anti-inflammatory effects and is effective against neuropathic pain. Several studies have shown that intravenous lidocaine may be associated with improved analgesia, reduced opioid consumption, shorter hospital stay, and decreased postoperative ileus, nausea, and vomiting-particularly in abdominal and genitourinary surgeries. Therefore, Intravenous (IV) lidocaine may be a valuable alternative for postoperative pain management after liver surgery.
National guidelines now recommend perioperative Intravenous (IV) lidocaine for abdominal surgeries but its efficacy in liver surgery has not yet been established due to a lack of specific evidence (more specific data are needed). Findings from other types of abdominal surgery suggest a potential benefit, which should be confirmed by dedicated clinical trials and robust multicenter evaluation such as the ILHEP protocol.
The goal of this clinical trial is to assess the effect of intravenous perioperative lidocaine on postoperative opioid related-side effects and to formally confirm the safety of lidocaine during hepatic surgical procedures. The hypothesis is that Intravenous (IV) lidocaine compared with placebo (a look-alike substance that contains no drug e.g. a saline solution) would improve postoperative outcome by reducing opioid related side-effects in patients undergoing liver surgery and benefitting of the same baseline analgesia.
In the context of this trial, patients will receive either intravenous lidocaine or placebo according to their assigned randomization group during standardized general anesthesia, and will then be followed throughout their hospital stay until discharge or up to a maximum of 28 days.
An ancillary study will be conducted in patients enrolled at the coordinating center in Rennes to assess exposure to lidocaine during intravenous administration and to evaluate the relationship between blood concentrations and adverse events.
Přehled studie
Postavení
Podmínky
Detailní popis
Patients scheduled for surgery under general anesthesia meeting the inclusion criteria will be eligible. During the preoperative anesthesia consultation (from Day-30 to Day-1), the investigator will present the study and the objectives of the research to the patient. When the patient arrives for admission, on the same day as the experimental visit or the day before (from Day-1 or Day 0), the investigator will verify the inclusion criteria and collect the written informed consent. Once inclusion has been validated, data will be collected : Socio-demographic data / Clinical data / List of chronic medications prior to surgery.
After signing the consent form and before the first dose of medication is taken, participants will be randomized into the control (placebo) or experimental group (lidocaine). In order to ensure group compatibility, a plan of randomization will be used : patients will be assigned to the treatment group in chronological order of randomization numbers, using a centralized randomization method via Ennov software (Ennov Clinical, Groupe Ennov, Paris, France). Randomization will be carried out online by investigators as close as possible to the surgery (Day-1 or Day 0). Participants and investigators will be blinded to the intervention.
Regarding the surgical procedure, general anesthesia will be standardized, and patients will receive either placebo or lidocaine according to the group to which they were assigned during randomization.
Physicians will be warned to reinject sufentanil or remifentanil during surgery in an opioid sparing spirit.
The postoperative protocol will be standardized. Extubation defines the Hour 0 for assessment of the primary criterion events. Aside from the placebo or lidocaine administered according to their randomization group, all patients will receive standard postoperative treatment.
An ancillary study will be conducted at the coordinating centre and is expected to include approximately 20 patients to assess drug exposure during perioperative intravenous lidocaine administration. It will also evaluate the relationship between maximal total and free concentrations (Cmax and Cmaxμ, measured at the end of the intravenous lidocaine bolus) and/or steady-state concentrations (Css and Cssμ, measured at the end of lidocaine administration) and the occurrence of adverse events. Blood samples (5 mL) will be drawn through a catheter:
- 5 minutes after the lidocaine or placebo bolus
- at the end of the lidocaine or placebo administration in post anesthesia care unit (PACU)
This trial is an intention to treat study, that is all randomized patients will be analyzed in their randomization group.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 4
Kontakty a umístění
Studijní kontakt
- Jméno: Alain CARO
- Telefonní číslo: +33299289496
- E-mail: alain.caro@chu-rennes.fr
Studijní záloha kontaktů
- Jméno: Pr Hélène BELOEIL, MD
- Telefonní číslo: +33299282422
- E-mail: helene.beloeil@chu-rennes.fr
Studijní místa
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Clermont-Ferrand, Francie, 63100
- Centre 03 - CHU de Clermont-Ferrand, Hôpital Estaing
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Kontakt:
- Ugo SCHIFF, MD
- Telefonní číslo: +33473755168
- E-mail: uschiff@chu-clermontferrand.fr
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Vrchní vyšetřovatel:
- Ugo SCHIFF, MD
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La Roche-sur-Yon, Francie, 85000
- Centre 04 - Centre Hospitalier Départemental de la Vendée
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Kontakt:
- Alexis DUCHALAIS, MD
- Telefonní číslo: +33251446237
- E-mail: alexis.duchalais@ght85.fr
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Vrchní vyšetřovatel:
- Alexis DUCHALAIS, MD
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Le Coudray, Francie, 28630
- Centre 02 - CH Louis Pasteur, Les Hôpitaux de Chartres
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Kontakt:
- Nidhal CHEBBI, MD
- Telefonní číslo: +33237303030
- E-mail: nchebbi@ch-chartres.fr
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Vrchní vyšetřovatel:
- Nidhal CHEBBI, MD
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Lille, Francie, 59000
- Centre 05 - CHU de Lille
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Vrchní vyšetřovatel:
- Gilles LEBUFFE, MD
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Kontakt:
- Gilles LEBUFFE, MD
- Telefonní číslo: +330320444508
- E-mail: gilles.lebuffe@chru-lille.fr
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Lyon, Francie, 69008
- Centre 06 - Centre Léon Bérard
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Kontakt:
- Grégoire WALLON, MD
- Telefonní číslo: +33478782971
- E-mail: gregoire.wallon@lyon.unicancer.fr
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Vrchní vyšetřovatel:
- Grégoire WALLON, MD
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Nice, Francie, 06200
- Centre 07 - CHU Nice, Hôpital Archet 2
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Kontakt:
- Romain ROZIER, MD
- Telefonní číslo: +33492036647
- E-mail: rozier.r@chu-nice.fr
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Vrchní vyšetřovatel:
- Romain ROZIER, MD
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Paris, Francie, 75013
- Centre 08 - AP-HP - Sorbonne Université, Hôpital de la Pitié-Salpêtrière
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Kontakt:
- Alexandre SITBON, MD
- Telefonní číslo: +33184827379
- E-mail: alexandre.sitbon@aphp.fr
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Vrchní vyšetřovatel:
- Alexandre SITBON, MD
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Rennes, Francie, 35000
- Centre 01 - CHU de RENNES, Hôpital Pontchaillou
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Kontakt:
- Pr Hélène BELOEIL, MD
- Telefonní číslo: +33299282422
- E-mail: helene.beloeil@chu-rennes.fr
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Vrchní vyšetřovatel:
- Pr Hélène BELOEIL, MD
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Toulouse, Francie, 31400
- Centre 09 - CHU Toulouse, Hôpital Rangueil
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Kontakt:
- Guillaume PORTA BONETE, MD
- Telefonní číslo: +33561323565
- E-mail: porta-bonete.g@chu-toulouse.fr
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Vrchní vyšetřovatel:
- Guillaume PORTA BONETE, MD
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
Inclusion Criteria:
- Inclusion criterion 1 : Age ≥ 18 years
- Inclusion criterion 2 : Undergoing a scheduled surgery for open hepatectomy
- Inclusion criterion 3 : Effective contraception in accordance with CFTG recommendations
- Inclusion criterion 4 : Having received oral and written information about the protocol and having signed a consent form to take part in this research
- Inclusion criterion 5 : Affiliated to a social security scheme
Exclusion Criteria:
- Exclusion criterion 1 : Weight > 100 kg
Exclusion criterion 2 : Allergy or contraindication to lidocaine or one of its excipients and, in particular:
- Known hypersensitivity to lidocaine hydrochloride, to amide-type local anesthetics, or to any of the excipients (sodium chloride, sodium hydroxide solution or concentrated hydrochloric acid solution, water for injection)
- Treatment with following antiarythmic medication : class I, class III or Sotalol
- Heart failure NYHA grade 3-4, AV-block >1, without pacemaker
- Acute porphyria
- Recurrent porphyrias
- Uncontrolled epilepsy / Seizure at enrollment
- Exclusion criterion 3 : Allergy to one of the drugs used for anaesthesia or one of their excipients
Exclusion criterion 4 : Nefopam contraindication and, in particular:
- Renal insufficiency (Creatinine clearance < 15 mL/min)
- Untreated glaucoma
- Uncontrolled epilepsy
- Allergy
Exclusion criterion 5 : Ketoprofen contraindication and, in particular:
- Renal insufficiency (Creatinine clearance < 50 mL/min)
- Inflammatory bowel disease
- Allergy
- Exclusion criterion 6 : Urgent surgery
- Exclusion criterion 7 : Transplant surgery or transplanted patients
- Exclusion criterion 8 : Surgery with planned regional anaesthesia
- Exclusion criterion 9 : Patient with a preoperative Sp02 < 95%
- Exclusion criterion 10 : Obstructive sleep apnea syndrome
- Exclusion criterion 11 : Severe hepatic insufficiency (Prothrombin Ratio < 15%)
- Exclusion criterion 12 : Patient with an ongoing opioid medication that will blur the results
- Exclusion criterion 13 : Adults under legal protection (safeguard of justice, curatorship, guardianship), persons deprived of their liberty, pregnant or breast-feeding women, minors, persons unable to express their consent, persons hospitalized for a different reason
- Exclusion criterion 14 : Known participation in other interventional research (RIPH1 or RIPH2)
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Podpůrná péče
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Trojnásobný
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: Lidocaine Group
Standard anaesthesia protocol with lidocaine
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Standard general anaesthesia induction protocol with pre-defined bolus of lidocaine and standard general anaesthesia maintenance protocol with pre-defined continuous intravenous infusion of lidocaine
Ostatní jména:
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Komparátor placeba: Control Group
Standard anaesthesia protocol with placebo (NaCl)
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Standard general anaesthesia induction protocol with pre-defined bolus of placebo and standard general anaesthesia maintenance protocol with pre-defined continuous intravenous infusion of placebo
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
To compare the effects of a perioperative lidocaine infusion versus placebo on the composite incidence of postoperative opioid-related adverse events, assessed blinded to the randomization group, in patients undergoing open hepatectomy.
Časové okno: from Hour 0 (extubation) to Hour 48
|
Number of participants with at least one of the following postoperative opioid-related adverse events : Postoperative nausea and vomiting defined as any nausea or vomiting ; Postoperative hypoxemia defined as SpO2 < 95% with a need for oxygen supplementation ; Postoperative ileus duration.
Ileus is defined as an intolerance to an oral diet (e.g.
soft food or light meal)
|
from Hour 0 (extubation) to Hour 48
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Determine the occurrence of postoperative opioid-related nausea and vomiting
Časové okno: from Hour 0 to Hour 48
|
Occurrence of postoperative opioid-related nausea and vomiting (the need for anti-emetic medication will also be recorded)
|
from Hour 0 to Hour 48
|
|
Determine the occurrence of postoperative opioid-related hypoxemia
Časové okno: from Hour 0 to Hour 48
|
Occurrence of postoperative opioid-related hypoxemia (duration of oxygen treatment will also be recorded)
|
from Hour 0 to Hour 48
|
|
Determine the occurrence of postoperative opioid-related ileus
Časové okno: from Hour 0 to Hour 48
|
Occurrence of postoperative opioid-related ileus
|
from Hour 0 to Hour 48
|
|
Determine the occurrence of postoperative opioid-related absence of flatus or stools
Časové okno: from Hour 0 to Hour 48
|
Occurrence of postoperative opioid-related absence of flatus or stools
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from Hour 0 to Hour 48
|
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Determine if lidocaine is associated with a better postoperative analgesia at rest, as measured by the number of episodes with a Numeric Rating Scale score > 3, recorded every 10 minutes during post anesthesia care unit stay and every 6 hours thereafter.
Časové okno: from Hour 0 to Hour 48
|
Number of episodes with Numeric Rating Scale score > 3 at rest Numeric rating scale : Zero is equivalent to no pain and 10 indicates the worst possible pain.
|
from Hour 0 to Hour 48
|
|
Determine if lidocaine is associated with a better postoperative analgesia at rest, as measured by the maximum Numeric Rating Scale score recorded.
Časové okno: from Hour 0 to Hour 48
|
Maximum Numeric rating scale score recorded at rest Numeric rating scale : Zero is equivalent to no pain and 10 indicates the worst possible pain.
|
from Hour 0 to Hour 48
|
|
Determine if lidocaine is associated with a better postoperative analgesia during movement, as measured by the number of episodes with a NRS score > 3, recorded every 10 minutes during Post-Anesthesia Care Unit stay and every 6 hours thereafter
Časové okno: from Hour 0 to Hour 48
|
Number of episodes with Numeric rating scale > 3 during movement Numeric rating scale : Zero is equivalent to no pain and 10 indicates the worst possible pain.
|
from Hour 0 to Hour 48
|
|
Determine if lidocaine is associated with a better postoperative analgesia during movement, as measured by the maximum Numeric Rating Scale score recorded.
Časové okno: from Hour 0 to Hour 48
|
Maximum Numeric rating scale score recorded during movement Numeric rating scale : Zero is equivalent to no pain and 10 indicates the worst possible pain.
|
from Hour 0 to Hour 48
|
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Determine if lidocaine can reduce postoperative opioid consumption
Časové okno: from Hour 0 to Hour 48
|
Opioid consumption (mg)
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from Hour 0 to Hour 48
|
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Determine if lidocaine can reduce the delay to obtain an Aldrete score ≥ 9 after extubation
Časové okno: from Hour 0 (extubation) to Post-Anesthesia Care Unit discharge, up to 24 hours
|
Time (minutes) between extubation (H0) and achieving an Aldrete score ≥ 9 Aldrete Scoring System consists of 5 clinically relevant parameters reflecting physiological recovery from anesthesia (muscle activity, respiration, circulation, consciousness, and color) ranging from 0 (no recovery) to 10 (full recovery). A total score of 0 indicates no recovery across the assessed criteria and reflects the poorest possible post-anesthesia status. A total score of 10 indicates full recovery across all assessed criteria, represents the best possible post-anesthesia status and is generally ready for discharge from the post-anesthesia care unit. |
from Hour 0 (extubation) to Post-Anesthesia Care Unit discharge, up to 24 hours
|
|
Determine if lidocaine reduces postoperative rate of unscheduled admission in intensive care unit (ICU)
Časové okno: from Hour 0 to Day 28
|
Rate of unscheduled admission in intensive care unit
|
from Hour 0 to Day 28
|
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Determine if lidocaine reduces the length of stay in the hospital
Časové okno: from Hour 0 to Day 28
|
Hospital length of stay (minutes)
|
from Hour 0 to Day 28
|
|
Determine if lidocaine reduces the incidence of the most frequent complications, particularly pneumonia
Časové okno: from Hour 0 to Day 7 or until hospital discharge, whichever occurs first; maximum Day 28
|
Occurrence of pneumonia episodes of newly confirmed pneumonia according to the modified Centers for Disease Control and Prevention (CDC) criteria.
|
from Hour 0 to Day 7 or until hospital discharge, whichever occurs first; maximum Day 28
|
|
Determine if lidocaine reduces the incidence of the most frequent complications, particularly acute kidney injury
Časové okno: from Hour 0 to Day 7 or until hospital discharge, whichever occurs first; maximum Day 28
|
Occurrence of acute kidney insufficiency defined with Kidney Disease Improving Global Outcomes (KDIGO) ≥ 2
|
from Hour 0 to Day 7 or until hospital discharge, whichever occurs first; maximum Day 28
|
|
Determine if lidocaine reduces the incidence of the most frequent complications, particularly the need for reintervention because of a surgical complication
Časové okno: from Hour 0 to Day 7 or until hospital discharge, whichever occurs first; maximum Day 28
|
Occurrence of reintervention because of surgical complication
|
from Hour 0 to Day 7 or until hospital discharge, whichever occurs first; maximum Day 28
|
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Determine if lidocaine reduces the incidence of the most frequent complications, particularly new onset of postoperative atrial fibrillation
Časové okno: from Hour 0 to Day 7 or until hospital discharge, whichever occurs first; maximum Day 28
|
Occurrence of a new onset of postoperative atrial fibrillation
|
from Hour 0 to Day 7 or until hospital discharge, whichever occurs first; maximum Day 28
|
|
Determine if lidocaine is associated with a better quality of recovery
Časové okno: from Hour 24 to Hour 48
|
Quality of recovery questionnaire QoR-40 is a 40-item questionnaire used to assess postoperative quality of recovery : the total score ranges from 40 (the worst possible recovery) to 200 (the best possible recovery).
|
from Hour 24 to Hour 48
|
|
Monitore the adverse effects of intravenous lidocaine
Časové okno: from Hour 0 to Hour 24
|
Number of adverse effects of intravenous experimental treatment
|
from Hour 0 to Hour 24
|
|
Evaluate drug exposure in 20 patients included in the coordinating center : relationship between maximal total plasma lidocaine concentration and the occurrence of adverse events
Časové okno: Perioperative/Periprocedural (5 minutes after the end of the IV lidocaine bolus)
|
Maximal total plasma lidocaine concentrations : Cmax , measured 5 minutes after the end of the IV lidocaine bolus
|
Perioperative/Periprocedural (5 minutes after the end of the IV lidocaine bolus)
|
|
Evaluate drug exposure in 20 patients included in the coordinating center : relationship between maximal free plasma lidocaine concentration and the occurrence of adverse events
Časové okno: Perioperative/Periprocedural (5 minutes after the end of the IV lidocaine bolus)
|
Maximal free plasma lidocaine concentrations : Cmaxμ, measured 5 minutes after the end of the IV lidocaine bolus
|
Perioperative/Periprocedural (5 minutes after the end of the IV lidocaine bolus)
|
|
Evaluate drug exposure in 20 patients included in the coordinating center : relationship between steady-state total plasma lidocaine concentration and the occurrence of adverse events
Časové okno: Day 0 (at the end of IV continuous lidocaine administration)
|
Steady-state total plasma lidocaine concentration : Css, measured at the end of IV continuous lidocaine administration
|
Day 0 (at the end of IV continuous lidocaine administration)
|
|
Evaluate drug exposure in 20 patients included in the coordinating center : relationship between steady-state free plasma lidocaine concentration and the occurrence of adverse events
Časové okno: Day 0 (at the end of IV continuous lidocaine administration)
|
Steady-state free plasma lidocaine concentration : Cssµ, measured at the end of IV continuous lidocaine administration
|
Day 0 (at the end of IV continuous lidocaine administration)
|
Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 35RC23_8878_ILHEP
- 2025-522462-73-00 (Ctis)
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Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
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