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 medications 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 its 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 measure
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 (if study stopped)
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
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
Basic results (scientific)
Publication list