Clinical Trial: Investigating a New Way of Giving Medicine to Newborn and Preterm Babies

Study Status: Terminated
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Oral Potassium Acid Phosphate Supplementation for Preterm Neonates; a Comparison of Oral Thin Films and Standard Oral Therapy.

Brief Summary: There is a deficit in the number of 'age-appropriate' formulations available for the delivery of medicines to children. Liquid preparations are considered the 'gold standard' for delivering medicines to children however many of these are formulated using ingredients which can be toxic to children (e.g. preservatives, alcohols), particularly to neonatal babies (< 4 weeks old) who do not possess the metabolic processes and mature organ function of older children or adults. Rapidly dissolving oral thin films (OTFs) dissolve quickly in the saliva, releasing the active ingredient(s) without the need for chewing or water, making them ideally suited to patients who find it difficult to swallow other oral dosage forms such as tablets or capsules. The aim of this study is to demonstrate that OTFs can offer a safe and effective alternative for oral administration of phosphate supplements to neonatal infants for the treatment of hypophosphataemia and osteopenia of prematurity. It is hypothesised that this treatment will be equal to standard therapy using an oral solution. Babies born before 32 weeks gestational age are routinely supplemented with oral phosphate as soon as they have been established on oral feeds in order to prevent bone disorders such as osteopenia. Babies recruited to this study will be given phosphate supplementation as per NHS Greater Glasgow and Clyde guidelines. This single-centre cross-over study will take place in the intensive care and special care baby units at the Princess Royal Maternity in Glasgow. The investigators aim to recruit 20-30 babies and will use blood phosphate levels (obtained from routine sampling only) to evaluate treatment effect. Babies will be randomised to receive either OTFs or oral solution of potassium acid phosphate for 2 weeks followed by 2 weeks of the other therapy. The investigators hypothesise that OTF treatment will be equivalent to standard oral solution.

Detailed Summary: There is a lack of 'age-appropriate' formulations available for delivering medicines to children. Liquid formulations are considered the 'gold standard' for delivering medicines to children. However, many of these are formulated using ingredients which can be toxic to children, and particularly to neonates (children <4 weeks old), who do not possess the metabolic processes and mature organ function of adults. For example, many liquid formulations contain preservatives such as benzoic acid to improve the shelf-life of the product, or include solvents such as propylene glycol or ethanol to improve solubility. Many of these additional, functional ingredients can product toxic effects in children. For example, neonates are unable to metabolise benzoic acid, resulting in the accumulation of this ingredient and potentially serious neurological and respiratory effects known as 'gasping syndrome'. Additionally, the lack of suitable licensed formulations for children leads to the routine prescribing of medicines outside the terms of their product license and/or the manipulation of medicines to make them suitable for children e.g. grinding up tablets. Further manipulation of products increases the risk of inaccurate dosages being administered, and adds a risk of error where additional calculations are required. There are also concerns over compatibility when medicines are, for example, mixed with foods or drinks in an attempt to improve acceptability. Looking specifically at prescribing within neonatal intensive care, up to 90% of medicines prescribed are unlicensed or off-label i.e. used in a way not covered by the product licence. Therefore, there is a need for more age-appropriate solid formulations suitable for delivering medicines to children. By formulating the medicine in a solid dosage form, the need for excipients such as preservatives can be removed. Within the last few years, rapidly dissolving oral thin films (OTFs) have been developed as a novel solid dosage p
Sponsor: University of Strathclyde

Current Primary Outcome: Serum phosphate [ Time Frame: Participants will be followed from birth until the end of the study period, approximately 6 weeks on average ]

The aim of this research is to demonstrate that oral thin films (OTFs) containing potassium acid phosphate are equivalent to standard oral phosphate supplementation using an oral solution in the prevention of hypophosphataemia (low blood phosphorus). The primary outcome measure will be plasma phosphate. We will assume an equivalent therapeutic effect using OTFs if individual plasma levels for these babies are found to lie within an acceptable physiological range, and the difference between the means of the two groups (as determined by a statistical t-test) lies within 20% of the mean plasma level for the control group.


Original Primary Outcome: Same as current

Current Secondary Outcome: Age-appropriateness [ Time Frame: Participants will be followed from birth until the end of the study period, approximately 6 weeks on average ]

Secondary objectives will be in terms of age-appropriateness and general acceptability. A lack of any observable adverse effects e.g. choking, vomiting, diarrhoea, will indicate the safety of oral thin films in this age group. Acceptability will be assessed in terms of observed discomfort/distress e.g. grimacing, crying, associated with treatment administration and will be assessed using visual analogue scales.


Original Secondary Outcome: Same as current

Information By: University of Strathclyde

Dates:
Date Received: August 23, 2012
Date Started: February 2013
Date Completion: November 2013
Last Updated: August 30, 2012
Last Verified: August 2012