Clinical Trials Register

Summary
EudraCT Number:	2017-003835-12
Sponsor's Protocol Code Number:	AC17067
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-01-24
Trial results	View 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

UK - MHRA

A.2

EudraCT number

2017-003835-12

A.3

Full title of the trial

A placebo controlled randomised trial of intravenous lidocaine in accelerating gastrointestinal recovery after colorectal surgery

A.3.1

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

A placebo controlled randomised trial of intravenous lidocaine in accelerating gastrointestinal recovery after colorectal surgery

A.3.2

Name or abbreviated title of the trial where available

ALLEGRO

A.4.1

Sponsor's protocol code number

AC17067

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	The University Of Edinburgh
B.1.3.4	Country	United Kingdom
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	National Institute of Health Research HTA programme
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Aberdeen
B.5.2	Functional name of contact point	Sarah Cameron
B.5.3	Address:
B.5.3.1	Street Address	3rd floor HSB, foresterhill
B.5.3.2	Town/ city	Aberdeen
B.5.3.3	Post code	AB25 2ZD
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01224438189
B.5.6	E-mail	sarah.cameron@abdn.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	NHS Lothian
B.1.3.4	Country	United Kingdom
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	The University of Aberdeen
B.5.2	Functional name of contact point	Sarah Cameron
B.5.3	Address:
B.5.3.1	Street Address	3rd floor Health Sciences Building
B.5.3.2	Town/ city	Aberdeen
B.5.3.3	Post code	AB25 2ZD
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01224438189
B.5.5	Fax number	01224438165
B.5.6	E-mail	sarah.cameron@abdn.ac.uk

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	No
D.2.1.1.1	Trade name	Lidocaine 2%
D.2.1.1.2	Name of the Marketing Authorisation holder	Tayside Pharmaceuticals
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.1	Product name	Lidocaine 2%
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 drip use (Noncurrent) Intravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lidocaine
D.3.9.1	CAS number	6108-05-0
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients scheduled for elective colorectal resection for colorectal cancer or diverticular disease.

E.1.1.1

Medical condition in easily understood language

Patients undergoing colorectal surgery for cancer or diverticular disease.

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10061451
E.1.2	Term	Colorectal cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10013534
E.1.2	Term	Diverticular disease
E.1.2	System Organ Class	100000004856

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10067878
E.1.2	Term	Bowel resection
E.1.2	System Organ Class	100000004865

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 primary aim is an effectiveness analysis to measure whether intravenous lidocaine (given at time of surgery) achieves faster return of gut function for more patients after colorectal surgery. The primary outcome will be the proportion of randomised subjects compared between IV lidocaine and placebo that have achieved return of gut function at 72 hours after their surgery. This will be measured by ‘GI-3 recovery’ -an endpoint defined as achievement of both of the following two events: tolerating diet (defined as ingestion of food and drink without significant nausea or vomiting for 3 consecutive meals) and passage of flatus OR stool (whichever comes first).

E.2.2

Secondary objectives of the trial

• to measure whether perioperative intravenous lidocaine is effective in achieving faster postoperative return of gut function measured by GI-2 recovery (defined as the time to the later of the following two events (both must be achieved): time to tolerating diet, and time to first passage of stool.
• to detect an absolute reduction of 10% (from 20% to 10%) in the rate of Prolonged Postoperative Ileus (PPOI= failure to establish GI-3 by postoperative day 5)
• to detect a reduction in postoperative nausea and vomiting
• to measure any difference in analgesia requirements
• to assess quality of postoperative recovery using multi-dimensional patient-reported outcome tools and quality of life tools, as well as assessing time to medically-defined and patient-defined readiness for discharge from hospital
• To measure the impact on recovery of variation in perioperative care from Enhanced Recovery after Surgery guidelines
• To assess whether perioperative intravenous lidocaine during colore

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients scheduled for elective colorectal resection for colorectal cancer or diverticular disease at participating UK colorectal surgery units.
Right hemicolectomy, extended right hemicolectomy, left colectomy, sigmoid colectomy, subtotal colectomy with ileosigmoid or ileorectal anastomosis and high anterior resection are eligible

E.4

Principal exclusion criteria

Planned epidural anaesthesia
Planned regional or local infiltration of lidocaine at the same time as lidocaine infusion
Current pregnancy or breast feeding
Age <18 years
Patients lacking capacity to give informed consent.
Known or suspected allergy to lidocaine or amide-type local anaesthetics
Current complete heart block
Current severe liver dysfunction (Child’s A or greater)
Current renal failure (eGFR<30)
Patients participating in the active intervention phase of another therapeutic clinical trial (or other interventional trial) unless a co-enrollment agreement is in place
Patients having surgery for indications other than colorectal cancer/diverticular disease
Rectal cancer below the peritoneal reflection in which total mesorectal excision is anticipated
Rectal cancer patients who have received any neoadjuvant radiotherapy
A preoperative surgical plan to form any new stoma during the primary procedure

E.5 End points

E.5.1

Primary end point(s)

The primary outcome will be the proportion of randomised subjects compared between IV lidocaine and placebo that have achieved return of gut function at 72 hours postoperatively.

E.5.1.1

Timepoint(s) of evaluation of this end point

72 hours

E.5.2

Secondary end point(s)

Time to return of gut function using the GI-3 recovery definition (a composite endpoint defined as time from surgery to the later time to establish both of the following two events: time to tolerating diet without significant nausea or vomiting for 3 consecutive meals and time to first passage of flatus or stool)
time from start of operation to event

Time to return of gut function using the GI-2 recovery definition (a composite endpoint defined as time from surgery to the later time to establish both of the following two events: tolerating solid food without significant nausea or vomiting for 3 consecutive meals and first passage of stool)
a) Yes/No outcome at 96 hours after start of operation; b) time to event
proportion of participants achieving GI-2 recovery at 96 hours;
96 hours after start of operation

Prolonged Postoperative Ileus (PPOI= failure to establish GI-3 by 120 hours after surgery (postoperative day 5))
Measurement variable: GI-3 recovery 120 hours after start of operation

Nausea and vomiting
Measurement variables: daily PONV score; number of episodes of vomiting/day (defined as episodes of expulsion of gastric content); total dosage of rescue antiemetic
PONV questionnaire: total number episodes vomiting within 72 hours of operation; total dose rescue antiemetic within 72 hours of operation
daily until 72 hours after start of operation

Quality of analgesia
Measured by OBAS score daily in-hospital up to and including postoperative day 7.

Total postoperative opioid consumption
morphine equivalent doses, cumulative total until 72 hours after start of operation

Quality of Recovery
Quality of recovery score (15-question patient-reported outcome measure) daily while in hospital until discharge; also days 7 and 30 by post

Quality of life assessment- EQ-5D daily in hospital, day 7, 30 days and 90 days after date of surgery

Measurement of specific enhanced recovery guideline variables that have been shown to impact GI recovery
Enhanced Recovery After Surgery protocol compliance measured by recording specific variables relevant to return of gut function. These are:
Avoidance of long-acting opioids for maintaining anaesthesia
Prescribed PONV prophylaxis for 48 hours
Restrictive IV fluid policy- aiming for euvolaemia, assessed by total IV fluid administration in 24 hours from start of anaesthesia and measuring patient weight pre- and 24 hours post op.
Early feeding- carbohydrate supplement drink on day of surgery and solid food from postoperative day 1 onwards
Early mobilisation- patients should be out of bed for 2 hours on day of surgery and 4-6 hours every day thereafter AND walking
Routine postoperative laxative prescription
No NGT immediately after surgery

Time to achievement of medical criteria for discharge
Time (days) to meeting medically-defined hospital discharge criteria (independent hydration/nutrition, adequate analgesia by oral route, independent mobilisation, return of gut function by GI-3 definition, no medical contraindication)
time to event (days)

Patient-reported assessment of readiness for discharge
Time (days) to patient-reported readiness for discharge (must also have achieved medical criteria for discharge as noted above)- assessed daily from day 2 onward

Tertiary Endpoints:
Total length of hospital stay
Complications/ safety analysis
Record linkage analysis of survival

E.5.2.1

Timepoint(s) of evaluation of this end point

up to 90 days

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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

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

The end of the study is the last clinical follow-up which is defined as the last participants last clinical data collection (day 90)

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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1