None listed
Conditions
Brief summary
Background: Persistent patent ductus arteriosus (PDA) is diagnosed when the ductus arteriosus fails to close after 72 hour of life. The shunting of the circulating blood volume from the systemic to the pulmonary circulation may cause pulmonary overflow and impaired end organ perfusion. Therefore, treatment of PDA is important to prevent these complications. Hypothesis: the oral paracetamol is better than the intravenous paracetamol in treatment of premature neonates with hemodynamically significant patent ductus arteriosus. General Objective To compare the efficacy and safety of intravenous paracetamol versus oral paracetamol in premature neonates with patent ductus arteriosus Specific Objectives 1. To compare the number of complete closure of patent ductus arteriosus (Echo verified) in premature neonates following treatment with oral paracetamol versus intravenous paracetamol 2. To determine the safety profile of oral paracetamol and intravenous paracetamol in premature babies with patent ductus arteriosus Trial Design Single centre, randomized control trial (RCT) involving premature neonates with gestational age of 26 – 33 weeks 6 days who are admitted to Neonatal Intensive Care Unit (NICU) Hospital Universiti Sains Malaysia in Kelantan, Malaysia. Patients who meet the inclusion criteria will be randomized and started on the 3 days course of investigational treatment. Parental consent will be taken before starting this study. Patients are randomly assigned to one of investigational treatment with allocation ratio of 1:1. Echocardiography assessment will be done after 24 hour complete treatment. If PDA remains open after first course, the patients will be treated with another course of similar route of investigational treatment. If PDA fails to close after second course, patient will be given the rescue therapy based on patient’s condition (ibuprofen/indomethacin) and they will be fully managed by the hospital neonatal team. After they complete second course of investigational treatment, either PDA close or still open post second treatment, they are considered complete our trial and we will monitor the complication until 30 days post completion of treatment. Subsequently, if they fail the rescue therapy, patient will undergo surgical/medical intervention based on their suitable condition and this will be fully managed by the neonatal team. Early complications during treatment and late complications during 30 days post completion treatment are observed to assess the safety of paracetamol in patent ductus arteriosus.
Interventions
Initial echocardiogram will be done by by the expert personnel (either medical officer or technician) - to assess the size of patent ductus arteriosus, left atrium / aortic ratio (LA/AO), and shunting direction of patent ductus arteriosus (PDA). If the patient fulfill the inclusion criteria and exclusion criteria and has hemodynamically significant PDA with echocardiography evidence, patient will be randomized for either treatment oral paracetamol or intravenous paracetamol.
Oral paracetamol wil
Initial echocardiogram will be done by by the expert personnel (either medical officer or technician) - to assess the size of patent ductus arteriosus, left atrium / aortic ratio (LA/AO), and shunting direction of patent ductus arteriosus (PDA). If the patient fulfill the inclusion criteria and exclusion criteria and has hemodynamically significant PDA with echocardiography evidence, patient will be randomized for either treatment oral paracetamol or intravenous paracetamol. Oral paracetamol will be administered orally either directly oral or through an orogastric tube at 15 mg/kg per dose in 6 hourly intervals for 3 consecutive days. The serving of medication will be signed and monitored on the patient’s medication chart. Echocardiography assessment will be done after 24 hour post completion of each course of the investigational treatment (last dose of the course) by the expert personnel (either medical officer or technician), verified by paediatric cardiologist. If echocardiography assessment showed PDA still open after first course of paracetamol treatment, patient will receive another course of similar route of paracetamol for 3 days and reassessment will be done after 24 hour complete treatment. If PDA fails to close after second course, patient will be given the rescue therapy based on patient’s condition (ibuprofen/indomethacin) and they will be fully managed by the hospital neonatal team. After they complete second course of investigational treatment, either PDA close or still open post second treatment, they are considered complete our trial and we will monitor the complication until 30 days post completion of treatment. Subsequently, if they fail the rescue therapy, patient will undergo surgical/medical intervention based on their suitable condition and this will be fully managed by the neonatal team
Sponsors
Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
No minimum to 2 Months
Healthy volunteers
No
Inclusion criteria
1. Patients born at between 26 to 33 weeks 6 days of gestation 2. Birth weight equal or more than 700g 3. Hemodynamically significant PDA (One of the clinical signs of PDA with one echocardiographic evidence of significant PDA) a. Clinical signs of PDA: i. Respiratory signs, including tachypnea, chest retraction, increased respiratory support, unable to wean down respiratory support ii. Physical signs, including tachycardia, murmur, hyperdynamic precordium, bounding pulse, wide pulse pressure (>25mmHg) iii. Signs of congestive heart failure, including cardiomegaly, hepatomegaly or pulmonary congestion b. Echocardiographic evidence: Ductal left to right shunt with i. ductal size > 1.5mm or ii. left atrium to aortic root ratio > 1.4
Exclusion criteria
1. Major congenital malformation 2. Presence of any other structural abnormality of the heart 3. Echocardiographic evidence of pulmonary hypertension 4. Fetal hydrops 5. Life threatening infection 6. Grade 4 intraventricular haemorrhage 7. Severe liver failure 8. Previous treatment with paracetamol, ibuprofen, any COX inhibitor for any purpose
Outcome results
None listed