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

ISRCTN ISRCTN74887957
DOI https://doi.org/10.1186/ISRCTN74887957
Secondary identifying numbers N/A
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

Study designRandomised pragmatic double-blind multicentre trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleSildenafil citrate suspension versus sildenafil citrate powder paper for reduction of pulmonary hypertension in children during cardiac catheterisation: a randomised pragmatic trial
Study objectivesIn 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(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) studiedPulmonary hypertension
InterventionPower 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Sildenafil citrate (SC)
Primary outcome measureThe 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 measures1. 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 study start date01/05/2008
Completion date01/11/2008

Eligibility

Participant type(s)Patient
Age groupChild
Lower age limit0 Years
Upper age limit18 Years
SexBoth
Target number of participants182
Key inclusion criteria1. 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 criteriaChildren 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 enrolment01/05/2008
Date of final enrolment01/11/2008

Locations

Countries of recruitment

  • Brazil

Study participating centre

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

Sponsor information

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

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

Website http://www.incqs.fiocruz.br
ROR logo "ROR" https://ror.org/04jhswv08

Funders

Funder type

Research organisation

Oswaldo Cruz Foundation (Brazil)

No information available

National Institute of Cardiology (Brazil)

No information available

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

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan