Clinical Trials Register

Summary
EudraCT Number:	2020-004584-11
Sponsor's Protocol Code Number:	10140021910007
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-12-24
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

Netherlands - Competent Authority

A.2

EudraCT number

2020-004584-11

A.3

Full title of the trial

Optimal postoperative Pain management After Lung surgery (OPtriAL): multi-centre randomised trial

A.3.1

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

Optimal pain management after a lung operation

A.3.2

Name or abbreviated title of the trial where available

OPtriAL

A.4.1

Sponsor's protocol code number

10140021910007

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	Maxima MC
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	ZonMw
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	Maxima MC
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	Maxima MC
B.5.2	Functional name of contact point	Louisa Spaans
B.5.3	Address:
B.5.3.1	Street Address	De Run 4600
B.5.3.2	Town/ city	Veldhoven
B.5.3.3	Post code	5504DB
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	310408887243
B.5.6	E-mail	louisa.spaans@mmc.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Ropivacaine
D.2.1.1.2	Name of the Marketing Authorisation holder	Aspen pharma trading limited
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Local use (Noncurrent) Perineural use
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	Comparator
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	levobupivacaine hydrochloride
D.2.1.1.2	Name of the Marketing Authorisation holder	Fresenius Kabi Nederland BV.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Epidural use
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: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	Bupivacaine
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Infiltration
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

Acute postoperative pain after lung surgery

E.1.1.1

Medical condition in easily understood language

Chest pain immediately after lung surgery

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10054711
E.1.2	Term	Postoperative pain
E.1.2	System Organ Class	100000004863

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main objective is to compare regional continuous paravertebral block (PVB), single shot multi-level intercostal nerve block (ICNB) and thoracic epidural analgesia (TEA) as pain relief techniques in order to provide safe, effective and efficient pain management after thoracoscopic lung surgery. This study will provide the evidence for an ERATS protocol to be implemented for the optimal analgesic technique after VATS anatomic lung resection taking into account pain scores and QoR.

E.2.2

Secondary objectives of the trial

not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients referred for anatomical lung resection (pneumonectomy, (bi)lobectomy or segmentectomy) with the intention of performing it by VATS or RATS are eligible for the trial. Adult patients older than 18 years who are able to give informed consent and fill out questionnaires in Dutch.

E.4

Principal exclusion criteria

Patients with contra-indications for TEA or PVB (infection at skin site, increased intracranial pressure, non-correctable coagulopathy, sepsis and mechanical spine obstruction) or allergic reactions to local anaesthetics will be excluded. Patients chronically using opioids for reasons not related to the operation will be excluded from the study since postoperative baseline opioid requirement will be higher and TEA remains the preferred technique for these patients. If, prior to the procedure, catheter placement during TEA is unsuccessful, a continuous PVB will be given during the procedure, and, if catheter placement during PVB is unsuccessful, a single shot multilevel ICNB will be used. Non-inferiority will be analysed based on intention-to-treat, as well as per-protocol analysis.
In case the lung surgeon estimates the operation to be performed through a thoracotomy technique instead of a VATS the patient will be excluded.

E.5 End points

E.5.1

Primary end point(s)

The NRS (0-10; 0= no pain, 10=worst imaginable pain) will be used to measure pain scores. The primary outcome measure for ‘non-inferiority’ is the proportion of NRS ≥4, defined as the number of NRS ≥4 episodes divided by the total amount of NRS pain scores obtained. A minimum of 11 NRS pain scores will be collected (at the recovery room (1), on the ward (10)). The primary outcome for ‘superiority’ is QoR measured with the QoR-15 questionnaire on POD 1 and POD 2. The QoR-15 will provide a continuous variable with a minimum score of 0 and maximum score of 150, and contains the most relevant questions concerning 5 domains (emotional status, physical comfort, psychological support, physical independence and pain) of overall well-being and recovery after surgery.

E.5.1.1

Timepoint(s) of evaluation of this end point

4 weeks

E.5.2

Secondary end point(s)

1) Pain scores during rest and mobilisation at baseline, in the morning, afternoon and evening on POD 0-3 and at 2-3 weeks follow-up;
2) Proportion of postoperative pain scores of NRS ≥4 during mobilization at POD 0-3;
3) QoR-15 pre-operatively (baseline), POD 0, POD 3 and at 2-3 weeks follow-up;
4) Cumulative use of systemic opioids and analgesics at POD 0-3;
5) Postoperative complications until 2-3 weeks follow-up, according to the Clavien-Dindo classification;
6) Hospitalization, defined as the total number of days in hospital after the surgical intervention (including readmissions within the first 30 postoperative days). The following standardised discharge criteria after surgery will be applied in all participating hospitals: normal intake of nutrition; independent mobility; absence of fever (<38 °C); and no presence of chest tube.
7) Patient satisfaction (5-point Likert scale: not at all satisfied, slightly satisfied, neutral, very satisfied and extremely satisfied);
8) Degree of mobility (1-4 scale: on the bed (1), to the chair (2), to the toilet (3), outside the patient’s hospital room(4));

E.5.2.1

Timepoint(s) of evaluation of this end point

4 weeks

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

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

control group (standard care): thoracic epidural anaesthesia

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

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

LVLS

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

E.8.9.2

In all countries concerned by the trial years

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:

400

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

171

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

571

F.4.2

For a multinational trial

F.4.2.1

In the EEA

571

F.4.2.2

In the whole clinical trial

571

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

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

2020-12-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-03

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

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