Clinical Trials Register

Summary
EudraCT Number:	2012-000200-15
Sponsor's Protocol Code Number:	PG-ON-09
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-04-17
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

Spain - AEMPS

A.2

EudraCT number

2012-000200-15

A.3

Full title of the trial

PHASE IV RANDOMIZED DOUBLE BLINDED AND MULTICENTER CLINICAL TRIAL FOR THE EVALUATION OF AN OXIGEN AND NITROUS OXIDE 50/50 MIXTURE USE IN RENAL COLIC TREATMENT BY AN EMERGENCY SERVICE.

ENSAYO CLÍNICO EN FASE IV RANDOMIZADO DOBLE CIEGO Y MULTICENTRICO PARA LA EVALUACIÓN DEL USO DE UNA MEZCLA DE OXÍGENO Y OXIDO NITROSO 50/50 EN EL TRATAMIENTO DEL COLICO RENAL EN EL SERVICIO DE URGENCIAS

A.3.1

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

Clinical Trial for the assessment of treatment efficacy with a gas mixture of equal parts (50/50) of nitrous oxide (N2O) and oxygen (O2) in renal colic.

Ensayo para la valoración de eficacia del tratamiento con un gas mezcla a partes iguales (50/50) de óxido nitroso (N2O) y oxígeno (O2) en el cólico nefrítico.

A.3.2

Name or abbreviated title of the trial where available

CLINICAL TRIAL FOR THE EVALUATION OF A MIXTURE O2 + N2O IN RENAL COLIC

ENSAYO CLÍNICO PARA LA EVALUACIÓN DE UNA MEZCLA O2 + N2O EN EL CÓLICO RENAL

A.4.1

Sponsor's protocol code number

PG-ON-09

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	Fundación de Investigación Biomédica. Instituto de Investigación Sanitaria del Hospital Universitario de la Princesa.
B.1.3.4	Country	Spain
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	FIB Hospital Universitario La Princesa
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fundacion de Investigacion Biiomedica
B.5.2	Functional name of contact point	Ana Maria Tello
B.5.3	Address:
B.5.3.1	Street Address	c/Diego de Leon 62
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28006
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3491520 22 00 17524
B.5.5	Fax number	+3491520 25 40
B.5.6	E-mail	anamaria.tello@salud.madrid.org

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	Entonox
D.2.1.1.2	Name of the Marketing Authorisation holder	AGA AB
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Oxido nitroso
D.3.2	Product code	N01AX63
D.3.4	Pharmaceutical form	Inhalation gas
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	71597
D.3.9.1	CAS number	10024-97-2
D.3.9.2	Current sponsor code	Entonox
D.3.9.3	Other descriptive name	NITROUS OXIDE
D.3.9.4	EV Substance Code	SUB03447MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	Aire Medicinal
D.2.1.1.2	Name of the Marketing Authorisation holder	Abello-Linde
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	aire medicinal
D.3.4	Pharmaceutical form	Inhalation gas
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	68510
D.3.9.1	CAS number	7782-44-7
D.3.9.2	Current sponsor code	Aire Medicinal
D.3.9.3	Other descriptive name	OXYGEN
D.3.9.4	EV Substance Code	SUB14733MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	21
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	68510
D.3.9.2	Current sponsor code	Aire medicinal
D.3.9.3	Other descriptive name	NITROGEN
D.3.9.4	EV Substance Code	SUB12541MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	78
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

RENAL COLIC

COLICO RENAL

E.1.1.1

Medical condition in easily understood language

RENAL COLIC

COLICO RENAL

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

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

Check whether the use of a mixture of oxygen and nitrous oxide 50/50 reduces time to decrease the pain and its intensity compared to conventional analgesic treatment.

Comprobar si el uso de una mezcla de oxígeno y óxido nitroso 50/50 reduce el tiempo para disminuir el dolor y la intensidad del mismo comparado con el tratamiento analgésico convencional.

E.2.2

Secondary objectives of the trial

Check if the gas mixture decreases the number of drugs needed to relieve pain, opioid use, how long the patient stays in the emergency department, the need for admission and performance of ultrasound. Also as an additional objective analyze the economic impact and patient satisfaction using this gas compared to conventional treatment.

Comprobar si dicha mezcla de gases disminuye el número de fármacos necesarios para disminuir el dolor, el uso de opiáceos, el tiempo que el paciente permanece en el servicio de urgencias, la necesidad de ingreso y de realización de ecografía. Así mismo como objetivo adicional analizaremos el impacto económico y sobre la satisfacción del paciente del uso de dicho gas frente al tratamiento convencional.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age ? 18 years.
Low back pain irradiated or not.
Colic in nature.
Pain by pressure in the same side of pain.

Edad ?18 años.
Dolor lumbar irradiado o no.
De carácter cólico.
Puñopercusión positiva en el mismo lado del dolor.

E.4

Principal exclusion criteria

Patients <18 years.
? Patients who do not meet criteria for the diagnosis of renal colic.
? Patients with allergy or intolerance to either drug used in the study (dexketoprofen, metamizol, metoclorpropamida and / or pethidine).
Pregnant patients, applying the usual clinical management of patients with suspected renal colic. Be considered as not pregnant the patient who has not presented late in their menstrual cycle and that denies the possibility of pregnancy and / or using effective contraception or menopausal patient.
? breast feeding patients.
? Patients with clinically significant psychiatric condition at the discretion of the physician.
? Patients with absolute or relative contraindication for the use of N2O/O2 50/50:
or unable to work and / or altered level of consciousness.
o pneumothorax.
or with significant abdominal distension and / or suspected bowel obstruction.
o severe bullous emphysema.
or a history of recent diving (in the last 7 days).
or have suffered a head injury.
o those who have made recent intraocular injection of gas (in the last 7 days).
o which they have made a surgical procedure in the middle ear.
or oxygen saturation <94%.
o known deficiency of vitamin B12 or folic

?Pacientes <18 años.
?Pacientes que no cumplan criterios para el diagnóstico de cólico nefrítico.
?Pacientes con alergia o intolerancia a alguno de los fármacos a utilizar en el estudio (dexketoprofeno, metamizol, metoclorpropamida y/o petidina).
?. Pacientes gestantes, aplicando el criterio clínico habitual en el manejo de los pacientes con sospecha de cólico nefrítico. Se considerará como no gestante a la paciente menopáusica o a aquella que no ha presentado retraso en su ciclo menstrual y que niega la posibilidad de embarazo y/o utiliza método anticonceptivo eficaz
? Pacientes dando lactancia materna
? Pacientes con patología psiquiátrica clínicamente relevante a criterio del facultativo.
?Pacientes con contraindicación absoluta o relativa para el uso de N2O/O2 50/50:
o Incapaces de colaborar y/o con alteración del nivel de conciencia.
o Con neumotórax.
o Con distensión abdominal importante y/o sospecha de obstrucción intestinal.
o Con enfisema bulloso severo.
o Con antecedentes de buceo reciente (en los 7 últimos días).
o Que hayan sufrido un traumatismo craneoencefálico.
o A los que se haya realizado inyección intraocular reciente de gas (en los 7 últimos días).
o A los que se les haya realizado un procedimiento quirúrgico en el oído medio.
o Con saturación de oxígeno <94%.
o Con déficit conocido de vitamina B12 o fólico

E.5 End points

E.5.1

Primary end point(s)

The main objective is to test whether the use of a mixture of oxygen and nitrous oxide 50/50 reduces the time to reduce pain and its intensity compared to conventional analgesic treatment, and patient satisfaction with treatment given prior at discharge.

El principal objetivo es comprobar si el uso de una mezcla de oxígeno y óxido nitroso 50/50 reduce el tiempo para disminuir el dolor y la intensidad del mismo comparado con el tratamiento analgésico convencional, así como la satisfacción del paciente con el tratamiento administrado previo al alta.

E.5.1.1

Timepoint(s) of evaluation of this end point

Main outcomes: pain intensity measured by VAS as well as patient satisfaction with treatment given prior to discharge

Variables principales: Intensidad del dolor medida por la escala EVA así como la satisfacción del paciente con el tratamiento administrado previo al alta.

E.5.2

Secondary end point(s)

Secondary objectives ascertain whether the mixture of gases decreases the number of drugs needed to relieve pain, opioid use, how long the patient stays in the emergency department, the need for admission and performance of ultrasound. Also as an additional objective and analyze the economic impact on patient satisfaction from the use of this gas compared to conventional treatment

Como objetivos secundarios comprobar si dicha mezcla de gases disminuye el número de fármacos necesarios para disminuir el dolor, el uso de opiáceos, el tiempo que el paciente permanece en el servicio de urgencias, la necesidad de ingreso y de realización de ecografía. Así mismo como objetivo adicional analizaremos el impacto económico y sobre la satisfacción del paciente del uso de dicho gas frente al tratamiento convencional

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary outcomes:
- Number of drugs to achieve symptomatic control.
- Degree of sedation as measured by Modified Observer's Assessment of Alertness Sedation Scale (OAA / S) .
- Number of patients requiring opioids.
- Side Effects.
- Time elapsed between admission and discharge from the emergency.
- Degree of patient satisfaction.
- Demographic variables: age, sex and race.
- Physical variables: blood pressure, heart rate, temperature and oxygen saturation.
- Investigations: X-ray of abdomen, white blood cell count, hemoglobin, creatinine, urinalysis and ultrasound (the latter only in cases deemed necessary by the clinician caring for the patient).

Variables secundarias:
- Número de fármacos para conseguir el control sintomático.
- Grado de sedación medido por Modified Observer?s Assesment of Alertness Sedation Scale (OAA/S)
- Número de pacientes que requirieron el uso de opiáceos.
- Efectos secundarios.
- Tiempo transcurrido entre el ingreso y el alta de urgencias.
- Grado de satisfacción del paciente.
- Variables demográficas: edad, sexo y raza.
- Variables físicas: presión arterial, frecuencia cardiaca, temperatura y saturación de oxígeno.
- Pruebas complementarias: radiografía de abdomen, recuento de leucocitos, hemoglobina, creatinina, análisis de orina y ecografía (esta última solo en los casos que se considere necesaria por parte del clínico que atiende al paciente).

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.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

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)

Yes

E.8.2.2

Placebo

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

on which the last subject completed the study follow-up visit

Fecha en la que el último sujeto completa la visita de seguimiento del estudio

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:

242

F.1.3

Elderly (>=65 years)

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