Clinical Trials Register

Summary
EudraCT Number:	2018-003284-62
Sponsor's Protocol Code Number:	012508
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:	2019-02-05
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

UK - MHRA

A.2

EudraCT number

2018-003284-62

A.3

Full title of the trial

A randomised, blinded, placebo controlled, Phase 2a study to evaluate the safety and efficacy of administering Regadenoson to patients with critical injury and signs of haemorrhagic shock

A.3.1

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

Rescue with Regadenoson (ReWiRe)

A.3.2

Name or abbreviated title of the trial where available

Rescue With Regadenoson (ReWiRe)

A.4.1

Sponsor's protocol code number

012508

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	Queen Mary University London
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	Bart's Charity
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	J P Moulton Charitable Foundation
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	Queen Mary University London
B.5.2	Functional name of contact point	Dr Mays Jawad
B.5.3	Address:
B.5.3.1	Street Address	5 Walden Street
B.5.3.2	Town/ city	London
B.5.3.3	Post code	E1 2EF
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	020 7882 7275
B.5.6	E-mail	research.governance@qmul.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	Yes
D.2.1.1.1	Trade name	Rapiscan
D.2.1.1.2	Name of the Marketing Authorisation holder	GE Healthcare AS
D.2.1.2	Country which granted the Marketing Authorisation	Norway
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	Rapiscan
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Regadenoson
D.3.9.1	CAS number	313348-27-5
D.3.9.3	Other descriptive name	synthetic A2A adenoreceptor agonist
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.6 to 2.4
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	Intravenous bolus use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cardiovascular collapse following traumatic haemorrhage

E.1.1.1

Medical condition in easily understood language

Heart failure caused by major bleeding after injury

E.1.1.2

Therapeutic area

Diseases [C] - Injuries, poisonings, and occupational diseases [C21]

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

Regadenoson is a medicine that dilates blood vessels within the muscle of the heart, and is currently used to enable doctors to visualise the blood supply to heart tissue. The drug works by stimulating a particular type of receptor found in the heart and blood vessels. In addition to dilating blood vessels and improving blood flow, this particular receptor is also thought to protect cells that are not receiving enough oxygen, such as in the case of severe bleeding following injury. Our research team have a developed an animal model that recreates severe bleeding in trauma. Using this model, we have demonstrated that Regadenoson improves the function of the heart, reduces the severity of shock (reduced blood flow), and lowers the amount of fluid needed in resuscitation. We now wish to carry out a Phase 2a study to test whether the use of Regadenoson in severely injured, bleeding trauma patients can provide similar benefits to patient outcomes.

We wish to determine whether Regadenoson

E.2.2

Secondary objectives of the trial

In addition to the above, we wish to explore the following:
• Change in lactate from baseline to 2 hours post-dosing
• h-FABP level on admission and 24 hours (+/- 12-hours)
• 24-hour fluid and transfusion requirements
• Lactate level at admission and 24 hours post-admission
• Blood pressure on admission
• MAP on admission
• Difference between lowest SBP PH and admission SBP
• Number of ACEs (defined as rhythm or, ECG changes when noted by clinical team).
• Daily SOFA score for days 1 to 7
• Daily CTCOFR for days 1 to 7
• Total number of vasopressor/inotrope days including vasopressor/inotrope type and dose up to day 28, discharge, or death
• Total length of hospital stay up to day 28, discharge, or death
• GOS-E at discharge
• Total length of critical care stay up to day 28, discharge, or death
• Mortality (2-hour, 24-hour, discharge/28-day whichever is sooner)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male
• Deemed to be aged ≥18 and ≤70 years
• Activated pre-hospital code-red criteria (activation criteria are: systolic blood pressure <90 mmHg, AND suspected haemorrhage).
• Started transfusion of at least 1 unit of PRBCs (or blood component equivalent)
• Is intubated and ventilated
• Patient has suffered a traumatic injury
• Is able to be randomised within 1 hour of the pre-hospital physician arriving at the scene of the injury

E.4

Principal exclusion criteria

• Patient suffered a traumatic cardiac arrest prior to screening
• Patients who are suspected to have shock due a non-haemorrhagic cause, as assessed by the pre-hospital care team
• Time of IMP/Placebo administration not attainable prior to admission to the receiving hospital
• Presence of obvious catastrophic traumatic brain injury or other non-survivable injury, diagnosed by the pre-hospital team
• Known or suspected pre-injury cardiac disease
• Known allergy to regadenoson

E.5 End points

E.5.1

Primary end point(s)

Blood lactate level 2 hours post IMP administration.

E.5.1.1

Timepoint(s) of evaluation of this end point

2 hours post IMP dosing.

E.5.2

Secondary end point(s)

• Change in lactate from baseline to 2 hours post-dosing
• h-FABP level on admission and 24 hours (+/- 12-hours)
• 24-hour fluid and transfusion requirements
• Lactate level at admission and 24 hours post-admission
• Blood pressure and MAP on admission
• Difference between lowest SBP PH and admission SBP
• Number of ACEs (defined as rhythm, ECG changes when noted by clinical team).
• SOFA score for days 1 to 7
• CTCOFR for days 1 to 7
• Total number of vasopressor/inotrope days including vasopressor/inotrope type and dose
• Total length of hospital stay.
• GOS-E at discharge
• Total length of critical care stay.
• Mortality (24-hour, discharge/28-day whichever is sooner).

E.5.2.1

Timepoint(s) of evaluation of this end point

as 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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

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

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 study definition is when 98 completed (received the intervention, reach the primary endpoint, 2 hours and not actively withdrawn) participants have been recruited, all surviving participants have completed 28-day mortality check and all samples have been analysed.

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