Clinical Trials Register

Summary
EudraCT Number:	2018-001485-42
Sponsor's Protocol Code Number:	NL65290.091.18
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-12-20
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2018-001485-42

A.3

Full title of the trial

RECOVER study: the effect of low- versus normal pressure pneumoperitoneum during laparoscopic colorectal surgery on the early quality of recovery with perioperative care according to the enhanced recovery principles.

Substudy: the effectiveness of low pressure pneumoperitoneum during laparoscopic colorectal surgery in preserving innate immune homeostasis by reducing peritoneal mesothelial cell injury.

Estudio RECOVER: Efecto de la presión pneumoperitoneo baja versus normal en la calidad de la recuperación precoz durante cirugía colorrectal laparoscópica en el marco de un programa de recuperación intensificada

Subestudio: la efectividad del neumoperitoneo a baja presión durante la cirugía colorrectal laparoscópica para preservar la homeostasis inmune innata al reducir la lesión de las células mesoteliales peritoneales.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

RECOVER study: the effect of lower pressure inside the abdomen during keyhole surgery of the intestine on early recovery after surgery.

Estudio RECOVER: el efecto de una presión más baja dentro del abdomen durante la cirugía laparoscópica del intestino en la recuperación temprana después de la cirugía.

A.3.2

Name or abbreviated title of the trial where available

RECOVER study

Estudio RECOVER

A.4.1

Sponsor's protocol code number

NL65290.091.18

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Radboudumc
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Merck Sharp & Dohme BV
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Radboudumc
B.5.2	Functional name of contact point	RECOVER study information
B.5.3	Address:
B.5.3.1	Street Address	Geert Grooteplein Zuid 10, route 618
B.5.3.2	Town/ city	Nijmegen
B.5.3.3	Post code	6525 GA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31617171996
B.5.6	E-mail	kim.albers@radboudumc.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Esmeron (Rocuroniumbromide)
D.2.1.1.2	Name of the Marketing Authorisation holder	NV Organon
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ROCURONIUM
D.3.9.3	Other descriptive name	ROCURONIUM BROMIDE
D.3.9.4	EV Substance Code	SUB10353MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Bridion
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme Limited
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SUGAMMADEX
D.3.9.1	CAS number	343306-79-6
D.3.9.3	Other descriptive name	SUGAMMADEX SODIUM
D.3.9.4	EV Substance Code	SUB32205
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Laparoscopic colorectal surgery

Cirugía colorrectal laparoscópica

E.1.1.1

Medical condition in easily understood language

Keyhole surgery of the large intestine

Cirugía laparoscópica del intestino grueso

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Main study: to establish the relationship between the use of low pressure pneumoperitoneum with deep neuromuscular blockade and the early quality of recovery after laparoscopic colorectal surgery with perioperative care according to the enhanced recovery principles.

Estudio principal: establecer la relación entre el uso de neumoperitoneo de baja presión con bloqueo neuromuscular profundo y la calidad temprana de la recuperación después de la cirugía colorrectal laparoscópica con cuidados perioperatorios de acuerdo con los principios de recuperación precoz.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

RECOVER PLUS: to establish the relationship between the use of low pressure pneumoperitoneum with deep neuromuscular blockade and innate immune function after laparoscopic colorectal surgery.

Version 2, 02-05-2018

RECOVER PLUS: para establecer la relación entre el uso de neumoperitoneo de baja presión con bloqueo neuromuscular profundo y la función inmune innata después de la cirugía colorrectal laparoscópica.

Versión 2, 02-05-2018

E.3

Principal inclusion criteria

- Scheduled for laparoscopic colorectal surgery with a primary anastomosis
- Age ≥ 18 years
- Obtained informed consent

- Cirugía colorrectal laparoscópica programado con anastomosis primaria.
- Edad ≥ 18 años
- Consentimiento informado obtenido

E.4

Principal exclusion criteria

- Insufficient control of the local language to read the patient information and to fill out the questionnaires
- Primary colostomy
- Neo-adjuvant chemotherapy (substudy)
- Chronic use of analgesics or psychotropic drugs
- Use of NSAIDs shorter than 5 days before surgery
- Known or suspected allergy to rocuronium of sugammadex
- Neuromuscular disease
- Indication for rapid sequence induction
- Severe liver- or renal disease (creatinine clearance <30ml/min)
- BMI >35 kg/m²
- Deficiency of vitamin K dependent clotting factors or coagulopathy

- Insuficiente control del idioma local para leer la información del paciente y completar los cuestionarios.
- Colostomía primaria
- Quimioterapia neoadyuvante (subestudio)
- Uso crónico de analgésicos o psicotrópicos.
- Uso de AINE menos de 5 días antes de la cirugía.
- Alergia conocida o sospechada al rocuronio de sugammadex
- Enfermedad neuromuscular
- Indicación de inducción de secuencia rápida.
- Enfermedad hepática o renal grave (aclaramiento de creatinina <30 ml / min)
- IMC> 35 kg / m²
- Deficiencia de factores de coagulación dependientes de la vitamina K o coagulopatía

E.5 End points

E.5.1

Primary end point(s)

Quality of recovery (QoR-40) questionnaire score
Substudy: mononuclear cell activity ex vivo measured as IL-6 and IL-10 production upon LPS stimulation.

Puntuación del cuestionario de calidad de recuperación (QoR-40)
Subestudio: actividad de células mononucleares ex vivo medida como producción de IL-6 e IL-10 tras estimulación con LPS.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 hours after surgery

24 horas después de la cirugía

E.5.2

Secondary end point(s)

• Quality of recovery-40 questionnaire score
• McGill Pain questionnaire
• RAND-36 general health questionnaire
• Pain at rest and pain on movement (NRS 0-10), is pain acceptable or unacceptable, referred shoulder pain yes/no
• Postoperative nausea and vomiting (NRS 0-10)
• Cumulative opiate, analgesic and anti-emetics use
• Length of hospital stay
• Post-operative complications
• Surgical conditions; the Surgical Rating Scale is used to quantify the quality of the surgical field during the pneumoperitoneum phase
• Time to reach discharge criteria

Substudy:
• Peritoneal mesothelial hypoxia as reflected by peritoneal HIF1α mRNA expression.
• Histological peritoneal mesothelial cell injury and plasma levels of DAMPs and cytokines.

• Calidad de la puntuación del cuestionario Recovery-40
• Cuestionario McGill Pain
• Cuestionario de salud general RAND-36
• Dolor en reposo y dolor en el movimiento (NRS 0-10), es dolor aceptable o inaceptable, dolor de hombro referido sí / no
• Náuseas y vómitos postoperatorios (NRS 0-10)
• Uso acumulativo de opiáceos, analgésicos y antieméticos.
• Duración de la estancia hospitalaria.
• Complicaciones postoperatorias
• Condiciones quirúrgicas; La Escala de Valoración Quirúrgica se utiliza para cuantificar la calidad del campo quirúrgico durante la fase de neumoperitoneo.
• Tiempo para alcanzar los criterios de alta

Subestudio:
• Hipoxia mesotelial peritoneal reflejada por la expresión peritoneal de ARNm de HIF1α.
• Lesión histológica de células mesoteliales peritoneales y niveles plasmáticos de DAMP y citocinas.

E.5.2.1

Timepoint(s) of evaluation of this end point

• Quality of recovery-40 questionnaire score day 3 and 7 after surgery
• McGill Pain and RAND-36 questionnaires upon admission and 3 months after surgery.
• Pain scores, nausea and vomiting 1, 8, 24 and 72 hours after surgery
• Cumulative opiate, analgesic and anti-emetics use and length of hospital stay at discharge
• Post-operative complications after 3 months
• Surgical conditions during pneumoperitoneum
• Time to reach discharge criteria at 8, 24, 48 and 72 hours after surgery

Substudy:
• Peritoneal mesothelial hypoxia: HIF1α mRNA expression before and after pneumoperitoneum phase.
• Histological peritoneal mesothelial cell injury before and after pneumoperitoneum phase, plasma DAMPs and cytokines upon admission, before and after pneumoperitoneum and 24h after surgery.

•Puntuación del Recovery-40 días 3 y 7 después de la cirugía
• Cuestionarios McGill Pain y RAND-36 al ingreso y 3 meses tras la cirugía.
• Puntuaciones de dolor, náuseas y vómitos 1, 8, 24 y 72 horas tras la cirugía.
• Uso de opiáceos, analgésicos y antieméticos y duración de la estancia hospitalaria al alta.
• Complicaciones postoperatorias tras 3 meses.
• Condiciones quirúrgicas durante el neumoperitoneo.
• Tiempo para alcanzar los criterios de alta: 8, 24, 48 y 72 horas tras la cirugía.

Subestudio:
• Hipoxia mesotelial peritoneal: expresión de ARNm HIF1α antes y después del neumoperitoneo.
• Lesión histológica de células mesoteliales peritoneales antes y tras la el neumoperitoneo, DAMP en plasma y citocinas al ingreso, antes y después de neumoperitoneo y 24 h tras la cirugía.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

LVLS

Última visita último paciente

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

300

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

300

F.4.2.2

In the whole clinical trial

300

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Ninguno

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-02-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-01-29

P. End of Trial
P.	End of Trial Status	Ongoing

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