Effectiveness of a sildenafil citrate suspension for pulmonary hypertension in children: a randomised pragmatic trial

ISRCTN	ISRCTN74887957
DOI	https://doi.org/10.1186/ISRCTN74887957
Protocol serial number	N/A
Sponsor	National Institute of Quality Control in Health - Oswaldo Cruz Foundation (Brazil)
Funders	Oswaldo Cruz Foundation (Brazil), National Institute of Cardiology (Brazil), Pharmaceutical Industrial Technology Lab from Federal University of Rio de Janeiro (Brazil)

Submission date: 30/01/2008
Registration date: 09/05/2008
Last edited: 09/05/2008

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Gisele Huf
Scientific

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

Study information

Primary study design	Interventional
Study design	Randomised pragmatic double-blind multicentre trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Sildenafil citrate suspension versus sildenafil citrate powder paper for reduction of pulmonary hypertension in children during cardiac catheterisation: a randomised pragmatic trial
Study objectives	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(s)	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.
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Sildenafil citrate (SC)
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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
Completion date	01/11/2008

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	0 Years
Upper age limit	18 Years
Sex	All
Target sample size at registration	182
Key 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
Key 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
Date of first enrolment	01/05/2008
Date of final enrolment	01/11/2008

Locations

Countries of recruitment

Brazil

Study participating centre

National Instutute of Quality Control in Health

Rio de Janeiro
21040-900
Brazil

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes