Condition category
Circulatory System
Date applied
30/01/2008
Date assigned
09/05/2008
Last edited
09/05/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Gisele Huf

ORCID ID

Contact details

National Instutute of Quality Control in Health
Oswaldo Cruz Foundation
Av. Brasil 4365
Manguinhos
Rio de Janeiro
21040-900
Brazil

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Sildenafil citrate suspension versus sildenafil citrate powder paper for reduction of pulmonary hypertension in children during cardiac catheterisation: a randomised pragmatic trial

Acronym

Study hypothesis

In Brazil, sildenafil citrate is the most accessible option for the treatment of PH and it is widely used in most hospitals. When licensing sildenafil for treatment of PH, the regulating agency kept it forbidden for people under 18 years old. In the absence of an appropriate pharmaceutical formulation for children, the staff usually crush the tablets to be added to liquid food. However, modifying a commercially available medication may lead to increased toxicity, undesirable side effects, decreased efficacy, poor patient compliance because of the medication’s taste and potential hazards to health care workers. Our study hypothesis is that a compounding suspension made by a pharmacist in controlled conditions will do better than the powder papers used in routine.

Ethics approval

The project was submitted to the Ethics Committee of the Oswaldo Cruz Foundation (ref: CAAE - 0068.0.011.000-07) and will also be submitted to the Ethics Committee of every participating hospital.

Study design

Randomised pragmatic double-blind multicentre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Pulmonary hypertension

Intervention

Power calculations:
60% of patients reduce at least 20% the mean pulmonary arterial pressure after using powder papers of Sildenafil citrate (SC). To demonstrate that at least 80% of patients would present 20% reduction after using SC suspension with an alpha error of 5% and power of 80% it would be necessary to recruit 182 patients. The pilot intends to recruit 20 patients.

Disease information:
Pulmonary hypertension (PH) is a haemodynamic and clinic disease characterised by a progressive increase of pulmonary vascular resistance and a decrease of pulmonary vascular capacitance leading to right ventricular failure and death. It may occur in isolation (idiopathic pulmonary arterial hypertension) or it may be associated to a variety of systemic disorders (scleroderma, lupus, human immunodeficiency virus [HIV] infection) or cardiopulmonary pathologies such as congenital heart disease. PH is a rare condition and secondary pulmonary arterial hypertension prevalence is less than 0.0001% (statistics about secondary pulmonary hypertension, 2007). Although severe pulmonary arterial hypertension is uncommon, the prognosis of these patients is life threatening and treatment options are limited.

Interventions:
A sildenafil citrate suspension developed from the crushed tablets will be compared with the powder papers usually given to the children.
1. Sildenafil citrate suspension: the suspension will be prepared from both commercially available tablets and sildenafil citrate powder and the formulation must be easy to prepare at hospital pharmacies. The physical, chemical and microbiology stability of this suspension will be accessed simulating in-use conditions and the ones established by Brazilian drug laws.
2. Sildenafil citrate powder papers: the powder papers will be prepared from the crushed commercial tablets and addition of a diluent. The tablets will be sent to a private pharmacy to compound sildenafil citrate 5 mg powder papers (sachets) as it’s already done as a routine.

Both arms will receive sildenafil citrate 0.2 mg/kg as a single dose during cardiac catheterisation.

Intervention type

Drug

Phase

Not Specified

Drug names

Sildenafil citrate (SC)

Primary outcome measures

The proportion of patients in each group that reduce pulmonary arterial hypertension in at least 20% twenty minutes after the administration of sildenafil citrate 0.2 mg/kg, during cardiac catheterisation.

Secondary outcome measures

1. At 20 minutes measured by cardiac catheterisation after administration of sildenafil citrate:
1.1. Pulmonary vascular resistance
1.2. Pulmonary vascular resistance/systemic vascular resistance
1.3. Oxygenation index or oxygen requirement
1.4. Cardiac output
1.5. Mean systemic arterial pressure and surgery indication based on the response to sildenafil
2. At 24 hours: any adverse events
3. At 2 months: cardiac surgery and death

Overall trial start date

01/05/2008

Overall trial end date

01/11/2008

Reason abandoned

Eligibility

Participant inclusion criteria

1. Children from 0 to 18 years old, either sex
2. Diagnosed as having PH associated with congenital heart disease
3. Needing cardiac catheterisation with sildenafil to evaluate the response to the drug as a decision criteria to cardiac surgery

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

182

Participant exclusion criteria

Children will be excluded if:
1. The clinician believes that sildenafil represents an additional risk for the patient
2. The carrier refuses to sign the informed consent

Recruitment start date

01/05/2008

Recruitment end date

01/11/2008

Locations

Countries of recruitment

Brazil

Trial participating centre

National Instutute of Quality Control in Health
Rio de Janeiro
21040-900
Brazil

Sponsor information

Organisation

National Institute of Quality Control in Health - Oswaldo Cruz Foundation (Brazil)

Sponsor details

Av. Brasil 4365
Manguinhos
Rio de Janeiro
21040-900
Brazil

Sponsor type

Research organisation

Website

http://www.incqs.fiocruz.br

Funders

Funder type

Research organisation

Funder name

Oswaldo Cruz Foundation (Brazil)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Institute of Cardiology (Brazil)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Pharmaceutical Industrial Technology Lab from Federal University of Rio de Janeiro (Brazil)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes