Clinical Trials Register

Summary
EudraCT Number:	2016-003406-14
Sponsor's Protocol Code Number:	UHNM1219
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-05-10
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

2016-003406-14

A.3

Full title of the trial

The Metoclopramoide and selective oral decontamination for Avoiding Pneumonia after Stroke (MAPS-2) Trial: a 2x2 double-blind, randomized controlled trial of metoclopramide and selective oral decontamination for the prevention of pneumonia in patients with dysphagia after an acute stroke.

A.3.1

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

Metoclopramide and selective oral decontamination for Avoiding Pneumonia after Stroke (MAPS-2)

A.3.2

Name or abbreviated title of the trial where available

MAPS-2: Metoclopramide and SOD mouth paste to prevent pneumonia vs 1

A.4.1

Sponsor's protocol code number

UHNM1219

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN14124645

A.5.4

Other Identifiers

Name:

HTA

Number:

14-49-154

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	University Hospital of North Midlands NHS Trust
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 for Health Research HTA
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 Hospital of North Midlands NHS Trust
B.5.2	Functional name of contact point	Professor Christine Roffe
B.5.3	Address:
B.5.3.1	Street Address	Institute for Applied Clinical Sciences, Guy Hilton Research Centre,Thornburrow Drive
B.5.3.2	Town/ city	Stoke-on-Trent
B.5.3.3	Post code	ST4 6QG
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01782671655
B.5.5	Fax number	01782671619
B.5.6	E-mail	christine.roffe@uhnm.nhs.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	Yes
D.2.1.1.1	Trade name	Metoclopramide
D.2.1.1.2	Name of the Marketing Authorisation holder	Hameln 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	Metoclopramide
D.3.2	Product code	PL 01502/0044
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	Nasogastric use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Metocolpramide
D.3.9.1	CAS number	364-62-5
D.3.9.2	Current sponsor code	N/A
D.3.9.4	EV Substance Code	AS1
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	5 to 5
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	No
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	Selective Oral Decontamination Mouth Paste
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Oral paste
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oromucosal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Amphotericin B
D.3.9.1	CAS number	1397-89-3
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	IU/mg international unit(s)/milligram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	939 to 939
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Colistin sulphate
D.3.9.1	CAS number	1264-72-8
D.3.9.4	EV Substance Code	AS4
D.3.10	Strength
D.3.10.1	Concentration unit	IU/mg international unit(s)/milligram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	22,400 to 22,400
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tobramycin sulphate
D.3.9.1	CAS number	32986-56-4
D.3.9.4	EV Substance Code	AS5
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	697 to 697
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
D.8.4	Route of administration of the placebo	Nasogastric use (Noncurrent)
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oromucosal paste
D.8.4	Route of administration of the placebo	Oromucosal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Stroke

We are testing two differnt intervetnions which could prevent pneumonia in stroke patietns. Prevention pneumonia could potentiallly speed up recovery and improve survival.

E.1.1.1

Medical condition in easily understood language

Stroke

We are testing two differnt intervetnions which could prevent pneumonia in stroke patietns. Prevention pneumonia could potentiallly speed up recovery and improve survival.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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	10035669
E.1.2	Term	Pneumonia aspiration
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

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	10061256
E.1.2	Term	Ischaemic stroke
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10019016
E.1.2	Term	Haemorrhagic stroke
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess whether metoclopramide and/or SOD reduce mortality in patients with dysphagia after stroke

E.2.2

Secondary objectives of the trial

To assess the effect of metoclopramide and SOD on secondary outcomes: clinical outcomes, pneumonia incidence, disability, safety and costs

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Adult patients (18 years and over) with a clinical diagnosis of acute stroke (as defined by the World Health Organization, excluding the requirement of a duration of 24 h or more)
2. Within 9 h of stroke onset (in wake-up stroke the onset is defined as the time the patient awoke or was found unless this is more than 12 h from last known well)
3. Moderate to severe neurological impairment with a NIHSS Score >=10
4. Unable to take a normal oral diet or fluids because
a. too drowsy to be assessed formally or
b. failed bedside assessment of swallowing

E.4

Principal exclusion criteria

1. Evidence of vomiting since stroke onset
2. Pre-existing swallowing problems
3. Known oesophageal pathology that might interfere with placement of a nasogastric tube (e.g. malignancy, achalasia, pharyngeal pouch or web)
4. Probable or definite pneumonia (abnormal chest exam or pyrexia >37.7 °C, or receiving antibiotic treatment at time of presentation)
5. Contraindications to metoclopramide (hypersensitivity to metoclopramide or any of the excipients (sodium chloride, citric acid monohydrate, sodium citrate, dilute hydrochloric acid, dilute sodium hydroxide, nitrogen, or water for injection), epilepsy, gastrointestinal obstruction, perforation, or haemorrhage, gastrointestinal surgery within the last week, Parkinson’s disease, treatment with levodopa or dopaminergic agonists, phaeochromocytoma or neuroleptic malignant syndrome or tardive dyskinesia or methaemoglobinaemia or NADH cytochrome –b5 deficiency),
6. Patients with severe liver disease (cirrhosis) or severe kidney disease (eGFR<30 L/min)[iv]
7. Known allergy to colistin (polymyxin E), tobramycin, aminoglycosides in general, or amphotericin B
8. Pregnant or breast feeding[v]
9. Other co-morbid conditions with a life expectancy of less than 3 months at the discretion of the clinical treating team
10. Inability to gain consent from the patient or a personal legal representative or refusal of consent

E.5 End points

E.5.1

Primary end point(s)

Mortality up to the end of the study

E.5.1.1

Timepoint(s) of evaluation of this end point

This wil be recorded at the end of the study (up to 24 months form entolment)

E.5.2

Secondary end point(s)

Secondary Endpoints

1. Pneumonia within 14 d
2. No of days of antibiotic treatment for pneumonia within the first 30 days
3. Neurological recovery (NIHSS) at 30 d
4. Disability at 90 d (mRS)
5.Quality of life at 90 d (EQ-5D™)

Health Economic Endpoints
Cost per death avoided over 90 days
QALYs gained over 90 days

Explanatory Endpoints
- Vomiting, hypoxia within 14 d
- White blood cell count, C-reactive protein, results of sputum cultures, antibiotic resistance, C. difficile, and antibiotic treatment to 30 d
- Return to oral feeding to 90 d

E.5.2.1

Timepoint(s) of evaluation of this end point

See time points above.

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

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.6.13.1

Other scope of the trial description

prevention

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

E.8.1.6

Cross over

E.8.1.7

Other

E.8.1.7.1

Other trial design description

Factorial

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.8.6 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

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