Condition category
Musculoskeletal Diseases
Date applied
15/01/2019
Date assigned
07/03/2019
Last edited
08/03/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Osteoporosis is a bone disease that occurs when the body loses too much bone, makes too little bone, or both. As a result, bones become weak and may break from a fall.

Frequently, calcium supplements are recommended for the prevention or the treatment of the osteoporosis.

The main objective of the present study is to confirm whether the treatment with the ossein-hydroxyapatite complex, a calcium supplement, is better tolerated than the treatment with calcium carbonate, another calcium supplement.

Who can participate?
Women in the perimenopausal period.

Perimenopause takes place over several years in advance of the menopause and can last for 4 to 8 years. Thus, women between 40 and 50 years that are in the perimenopausal period, according to their physicians, are included in the study.

Women with normal bone density or slightly reduced (what is called osteopenia) are included in the study.

What does the study involve?
As the study compares two different calcium supplements, a group of participants is treated with 2 tablets every 12 hours of ossein-hydroxyapatite complex, a calcium supplement, and the other with 1 tablet every 12 hours of calcium carbonate, another calcium supplement. In all the patients the treatment is taken through the mouth. The treatment will last for three years.

What are the possible benefits and risks of participating?
Participants enrolled in this study are receiving a treatment that could help them to prevent osteoporosis.

The studied treatments are usually well tolerated. Nevertheless, some people could have constipation, mild nausea, diarrhoea, abdominal disturbances and, very rarely, itchy skin.

Where is the study run from?
The study has been developed in different health centers in an outpatient setting, previously specified, of several Spanish cities (A Coruña, Alicante, Badajoz, Barcelona, Bilbao, Santander, Castellón, Guadalajara, Las Palmas, León, Lugo, Madrid, Murcia Tarragona, Valencia, Zamora and Zaragoza).

When is the study starting and how long is it expected to run for?
The study begun in 2002 and patient inclusion finished in 2008.

Who is funding the study?
The study is funded by Pierre Fabre Ibérica S.A.

Who is the main contact?
José Manasanch
(jose.manasanch@pierre-fabre.com)

Trial website

Contact information

Type

Scientific

Primary contact

Dr José Manasanch

ORCID ID

http://orcid.org/0000-0003-3633-8778

Contact details

Ramon Trias Fargas
7-9
Barcelona
08005
Spain

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

PROP-02A

Study information

Scientific title

Pharmacovigilance observational study of two calcium supplements in the prophylaxis of the osteoporosis in the perimenopause: a longitudinal study

Acronym

PROP

Study hypothesis

To confirm that ossein-hydroxyapatite complex shows a higher tolerability than calcium carbonate.

Ethics approval

The study did not require ethics approval at the time of initiation as in 2002, in Spain, ethics approval was not mandatory for observational studies related to pharmacovigilance using registered and marketed calcium supplements in an approved indication.

It was approved by the Spanish Medicines Agency, Ministry of Health on the 05/03/2002.

Study design

Observational, multicentre, prospective, open-label, comparative study with a follow-up of three years.

Primary study design

Observational

Secondary study design

Longitudinal study

Trial setting

Community

Trial type

Prevention

Patient information sheet

No participant information sheet available.

Condition

Osteopenia

Intervention

Patients in the ossein-hydroxyapatite complex (OHC) arm took two tablets of OHC every 12 hours (830 mg OHC per tablet), by oral route, along three years.

Patients in the calcium carbonate (CC) group took one tablet every 12 hours (1,250 CC mg per tablet), by oral route, along three years.

As an observational study, carried out in the real-world practice, there were no randomisation.

Intervention type

Supplement

Phase

Drug names

Primary outcome measure

Measured using patient interview at follow-up visits every 6 months for 3 years:
1. The number of patients with at least one adverse reaction
2. The severity of the adverse reaction.
3. The relationship of the adverse reaction with the study medication
4. The actions taken in response to the adverse reaction.
5. The outcome of the adverse reaction.
6. The duration of the adverse drug reaction

Secondary outcome measures

1. Bone mineral density was measured by DEXA every 18 months.
2. BMI (kg/m2) was measured every 18 months.
3. The waist hip ratio (%) was measured every 18 months.
4. Lipid metabolism was measured using laboratory analytical data yearly.
5. Bone fractures taking place during the study period were registered at each 6-month follow-up visit.
6. Climacteric (menopausal) symptom changes were measured using the GEM scale every 18 months.
7. Treatment compliance was assessed by means of patient interview at each follow-up (every 6 months).

Overall trial start date

03/09/2001

Overall trial end date

12/07/2011

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Patients with an indication for the use of CC or OHC according to the investigator criteria.
2. Perimenopausal women between 40 and 50 years old.
3. Patients treated in an outpatient setting.

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Initially 1,024 patients were expected to be included in the study.

Participant exclusion criteria

1. Patients with severe osteopenia (diagnosed by DEXA, bone mineral density [BMD] ≤ -2 standard deviation [SD] T-score) or osteoporosis (BMD ≤ -2.5 SD T score)
2. Patients who were being treated with a drug that could have compromised bone metabolism such as: glucocorticoids, steroids, thyroid hormones, heparins (in long-term treatment), anticonvulsants, anovulatory drugs, hormone replacement therapy, lithium, chemotherapy, selective estrogen-receptor modulator (SERM), immunosuppressive therapy, and bisphosphonates. A minimal washout period of 6 months was established for any of the previous treatments prior to including the patient in the study.
3. Patients with severe hypercalcaemia or hypercalciuria.
4. Pregnant patients.
5. Concomitant diseases that could have affected bone metabolism: acromegaly, hyperthyroidism, primary hyperparathyroidism, anorexia nervosa, Cushing’s syndrome, rheumatoid arthritis, renal diseases, renal lithiasis, diabetes mellitus, and chronic liver disease.
6. Concomitant metabolic bone disease: osteomalacia, Paget’s disease.
7. Neoplastic disease developed in the last 5 years, with the exception of skin neoplasias treated with a radical treatment.
8. Known allergy to any compound of the study drugs.
9. Gastrointestinal disorders that could interfere with drug absorption.
10. Women with an expected difficult follow-up due to psychological, cognitive or social circumstances.
11. Patients with foreseen low compliance, difficult follow-up and/or poor collaboration, or with foreseen risk of withdrawal over a minimum period of 3 months due to dementia, alcoholism, terminal illness, etc.

Recruitment start date

25/07/2002

Recruitment end date

02/06/2011

Locations

Countries of recruitment

Spain

Trial participating centre

Centro Ntra Sra Belén
Teniente Coronel Teijeiro, 3
A Coruña
15011
Spain

Trial participating centre

H G U Alicante
Pintor Baeza, 11
Alicante
03010
Spain

Trial participating centre

H Alcoy
Caramanxel, s/n
Alcoy
03804
Spain

Trial participating centre

Clinica ginecológica
Padre Manjon, 15
Alicante
03600
Spain

Trial participating centre

Clínica ginecológica
Rbla Mendez Nuñez, 43
Alicante
03002
Spain

Trial participating centre

H Don Benito
Ctra. Don Benito-Villanueva, Km 3
Don Benito
06400
Spain

Trial participating centre

Clínica ginecológica
Rosselló, 161
Barcelona
08036
Spain

Trial participating centre

H Mar
P Marítim Barceloneta, 25
Barcelona
08003
Spain

Trial participating centre

Marti-Julia
Av Baix Llobregat, 17
Barcelona
08940
Spain

Trial participating centre

Centro Casagemas
Riera de Matamoros, s/n
Barcelona
08911
Spain

Trial participating centre

Clínica ginecológica
Av. Constitució, 177
Castelldefels
08860
Spain

Trial participating centre

Doctor Barraquer
Dr. Trueta, s/n
Barcelona
08930
Spain

Trial participating centre

Clin Quiron Barcelona
Alfonso Comín, 5
Barcelona
08023
Spain

Trial participating centre

Clínica ginecológica
Gordóniz Kalea, 6
Bilbao
48010
Spain

Trial participating centre

H U Marqués Valdecilla
Valdecilla, 25
Santander
39008
Spain

Trial participating centre

C E Jaime I
Trullols, 3
Castellón
12001
Spain

Trial participating centre

H G Castellon
Av Benicàssim, s/n
Castellón
12004
Spain

Trial participating centre

H U Guadalajara
Donante de Sangre, s/n
Guadalajara
19002
Spain

Trial participating centre

H U Materno-Infantil
Av Marítima del Sur, s/n
Las Palmas G. Canaria
35016
Spain

Trial participating centre

Clin N S Perpetuo Socorro
Leon y Castillo, 407
Las Palmas G. Canaria
35007
Spain

Trial participating centre

H León
Altos de Navas, s/n
León
24008
Spain

Trial participating centre

H Materno-Infantil
Dr Severo Ochoa, s/n
Lugo
27004
Spain

Trial participating centre

H Sta. Cristina
Amadeo Vives, 2
Madrid
28009
Spain

Trial participating centre

H La Paz
P Castellana, 261
Madrid
28046
Spain

Trial participating centre

CMS Tetuán
Aguileñas, 1
Madrid
28029
Spain

Trial participating centre

H U Mostoles
Río Júcar, s/n
Móstoles
28934
Spain

Trial participating centre

H M Central de la Defensa
Glor Ejército, 1
Madrid
28047
Spain

Trial participating centre

Clínica ginecológica
Angeles, 16
Torrelodones
28250
Spain

Trial participating centre

H U Getafe
Ctra Madrid - Toledo, Km 12.500
Madrid
28905
Spain

Trial participating centre

Inst Palacios
Antonio Acuña, 9
Madrid
28009
Spain

Trial participating centre

H Ramón y Cajal
Ctra Colmenar Viejo, Km 9,1
Madrid
28034
Spain

Trial participating centre

Clínica ginecológica
Jabonerías, 9
Murcia
30001
Spain

Trial participating centre

Clínica Monegal
Av President Companys, 12
Tarragona
43005
Spain

Trial participating centre

Clínica ginecológica
Av Blasco Ibáñez, 108
Valencia
46021
Spain

Trial participating centre

C E Monteolivete
Escultor José Capuz, 13
Valencia
46006
Spain

Trial participating centre

H Arnau Vilanova
Sant Clement, 12
Valencia
46015
Spain

Trial participating centre

Clínica ginecológica
Bèlgica, 1
Valencia
46021
Spain

Trial participating centre

H U La Ribera
vCtra. Corbera, km 1
Alzira
46600
Spain

Trial participating centre

Clínica ginecológica
Moralets, 21
Torrent
46900
Spain

Trial participating centre

Clínica reumatológica
Dr Manuel Candela, 41
Valencia
46021
Spain

Trial participating centre

C E Trinitat
La Flora, 7
Valencia
46010
Spain

Trial participating centre

Clínica ginecológica
Alfonso Peña, 7
Zamora
49010
Spain

Trial participating centre

Pol Adeslas
Carmen, 22
Zaragoza
50005
Spain

Trial participating centre

Centro Med Zaragoza
Gran Vía, 27
Zaragoza
50006
Spain

Trial participating centre

Clinica Aisa
P San Lamberto, 10
Zaragoza
50004
Spain

Sponsor information

Organisation

Javier Haya Palazuelos

Sponsor details

Sicomoro
11
Getafe
28903
Spain

Sponsor type

Other

Website

Funders

Funder type

Industry

Funder name

Pierre Fabre Ibérica, S.A.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Results about safety and efficacy are intended to be published, along 2019, in a peer-reviewed medicine journal addressed to clinicians of several specialities.

IPD sharing statement: the datasets generated during and/or analysed during the current study are/will be available upon request from José Manasanch, jose.manasanch@pierre-fabre.com.

The data (raw data and statistical analysis) will become available as soon as the results will be published and could be requested for a minimum of three years after this date if needed for investigational purposes. A formal request will be necessary.

Patients meeting the selection criteria were included in the study after providing informed consent that remain in the investigator files. Any data from the patients was anonymized from inclusion in the study.

Intention to publish date

21/06/2019

Participant level data

Available on request

Basic results (scientific)

See additional file (ISRCTN83573042_BasicResults_22Jan19)

Publication list

2015 results presented at EMAS Congress 2015: https://doi.org/10.1016/j.maturitas.2015.02.206

Publication citations

Editorial Notes

08/03/2019: Internal review. 07/03/2019: The basic results of this trial have been uploaded as an additional file