Clinical Trials Register

Summary
EudraCT Number:	2010-022468-11
Sponsor's Protocol Code Number:	ULTIMA08
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-09-20
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2010-022468-11

A.3

Full title of the trial

Ultrasound Accelerated Thombolysis of Pulmonary Embolism

A.3.1

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

Ultrasound Accelerated Thombolysis of Pulmonary Embolism (ULTIMA)

Ultraschall beschleunigte Thrombolyse bei Lungenemboliele

A.3.2

Name or abbreviated title of the trial where available

ULTIMA

A.4.1

Sponsor's protocol code number

ULTIMA08

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	EKOS Corporation
B.1.3.4	Country	United States
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	EKOS Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dr. Hans-Joachim Lau - Consultant
B.5.2	Functional name of contact point	Hans-Joachim Lau
B.5.3	Address:
B.5.3.1	Street Address	Airport Center (Haus C), Flughafenstraße 52a
B.5.3.2	Town/ city	Hamburg
B.5.3.3	Post code	22355
B.5.3.4	Country	Germany
B.5.4	Telephone number	00491608576962
B.5.5	Fax number	00494053299100
B.5.6	E-mail	hjlau@meddevconsult.de

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	Actilyse
D.2.1.1.2	Name of the Marketing Authorisation holder	Boehringer Ingelheim, Germany
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Actilyse
D.3.4	Pharmaceutical form	Powder and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraarterial use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALTEPLASE
D.3.9.1	CAS number	105857236
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	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	only for information to D.3.11.2: manufactured using gene technology from ovarial cell cultures of the chinese hamster

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

Patients with acute symptomatic PE confirmed by contrast-enhanced chest CT with embolus located in at least one main or proximal lower lobe pulmonary artery and an end-diastolic diameter RV/LV ratio > 1.0 on echocardiography

E.1.1.1

Medical condition in easily understood language

Pulmonary Embolism

E.1.1.2

Therapeutic area

Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	PT
E.1.2	Classification code	10037377
E.1.2	Term	Pulmonary embolism
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal 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

In patients with documented PE and right heart dysfunction, determine if treatment with ultrasound accelerated thrombolysis will significantly improve right heart function at 24 hours compared to patients receiving anticoagulation alone.

E.2.2

Secondary objectives of the trial

1) Determine PE symptoms at 24 hours and at 90 days,
2) Evaluate right heart function by echocardiography at 90 days,
3) Determine exercise capacity by 6-minute walk test at 90 days

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients with acute PE symptoms < 14 days.
2. Filling defect by contrast-enhanced chest CT in at least one main or proximal lower lobe pulmonary artery (see also Appendix 2 “Indications for the placement of one or two EkoSonic catheters by contrast-enhanced chest CT”)
3. Right ventricular dysfunction confirmed by echocardiography where the RV/LV end diastolic diameter ratio is ≥ 1.0.

E.4

Principal exclusion criteria

1. Age less than 18 years or greater than 80 years
2. Index acute PE symptom duration > 14 days
3. Insufficient echocardiographic image quality in the apical or subcostal four-chamber view that prohibits the measurement of the right and left ventricular end-diastolic dimensions
4. Known significant bleeding risk
5. Administration of thrombolytic agents within the previous 4 days
6. Active bleeding
7. Known bleeding diathesis
8. Known coagulation disorder platelet count < 100.000/mm³, or previous use of vitamin K antagonists with INR <2.5
9. History of any intracranial or intraspinal surgery or trauma or intracranial/intraspinal bleed
10. Intracranial neoplasm, arteriovenous malformation, or aneurysm
11. Recent (< 3 months) GI bleeding.
12. Recent (< 3 months) internal eye surgery or hemorrhagic retinopathy; recent (< 10 days) major surgery, cataract surgery, trauma, CPR, obstetrical delivery, or other invasive procedure.
13. Allergy, hypersensitivity, or thrombocytopenia from heparin, rt-PA, or iodinated contrast, except for mild-moderate contrast allergies for which steroid pre-medication can be used.
14. Glomerular filtration rate (eGFR) < 50 ml/min as calculated by the Cockroft formula.
15. Hemodynamic collapse at presentation defined as: need for cardiopulmonary resuscitation; or systolic blood pressure < 90 mm Hg for at least 15 min, or drop of systolic blood pressure by at least 40 mm Hg for at least 15 min with signs of end organ hypoperfusion (cold extremities or low urinary output < 30 mL/h or mental confusion); or need for catecholamine administration to maintain adequate organ perfusion and a systolic blood pressure of > 90 mm Hg.
16. Severe hypertension on repeated readings (systolic > 180 mmHg or diastolic > 105 mmHg).
17. Pregnant, lactation or parturition within the previous 30 days (positive pregnancy test, women of childbearing age must be tested ).
18. Participating in any other investigational drug or device study.
19. Life expectancy < 90 days.
20. Inability to comply with study assessments (e.g. due to geographic distance).
21. Previous enrollment in this study
22. Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated.
23. Known right-to-left shunt, for example from large patent foramen ovale or atrial septal defect
24. Large (>10 mm) right atrial or right ventricular thrombus

E.5 End points

E.5.1

Primary end point(s)

7 EFFICACY OUTCOMES
7.1 Primary Efficacy Outcome
Change in the end-diastolic RV/LV ratio from baseline to 24 hours by echocardiography.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 hours

E.5.2

Secondary end point(s)

7.2 Secondary Efficacy Outcomes
1) PE symptoms at 24 hours and at 90 days,
2) Right heart function by echocardiography at 90 days,
3) Exercise capacity by 6-minute walk test at 90 days.

8 SAFETY OUTCOMES
• Major bleeding at 30 days (see definitions below).
• Intracranial bleeding at 30 days.
• Haemodynamic collapse at discharge
• need for cardiopulmonary resuscitation; or
• systolic blood pressure < 90 mm Hg for at least 15 min, or
• drop of systolic blood pressure by at least 40 mm Hg for at least 15 min with signs of end organ hypoperfusion (cold extremities or low urinary output < 30 mL/h or mental confusion); or
• need for catecholamine administration to maintain adequate organ perfusion and a systolic blood pressure of > 90 mm Hg (including dopamine at the rate of > 5 micrograms / kg per minute)
• Recurrent symptomatic pulmonary embolism at 90 days.
• Mortality at 90 days.

E.5.2.1

Timepoint(s) of evaluation of this end point

24 hours and 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

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)

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

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

Yes

E.8.2.3.1

Comparator description

standard of care, anticoagulant therapy (heparine)

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Switzerland

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

End of trial is last patient last follow-up completed (90 days individual follow-up).

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.1.1.1

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

F.4.2.2

In the whole clinical trial

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)

after exiting the trial the patients will be followed by standard care for their disease status.

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

2010-10-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-11-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-04-12

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials