Name: a clinical trial assessing the safety, efficacy, and delivery of olive-oil-based three-chamber bags for parenteral nutrition
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Description: Watch this Scientific Journal Video about A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition at JoVE.com

The study was sponsored and funded by Baxter Healthcare, manufacturer/Licensee of OliClinomel N4. ProScribe was used in compliance with global guidelines for good publication practice.

For this prospective, randomized, multicenter, active-controlled, parallel-group investigational trial, the Ethics Committees of Shanghai Sixth People&#8217;s Hospital approved the study protocol.
1. Patient recruitment and enrollment
<ol>
	<li>Recruit patients as per the inclusion criteria specified in the protocol. Seek informed consent from patients and perform screening assessments not more than 3 days prior to the scheduled surgery.</li>
	<li>Randomize enrolled subjects to one of the tw...

<ol>
	<li>Jeejeebhoy, K. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parenteral+nutrition+in+the+intensive+care+unit.">Parenteral nutrition in the intensive care unit.</a> Nutrition Reviews. 70 (11), 623-630 (2012).</li><li>Simmer, K., Rakshasbhuvankar, A., Deshpande, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standardised+parenteral+nutrition.">Standardised parenteral nutrition.</a> Nutrients. 5 (4), 1058-1070 (2013).</li><li>Vanek, V. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A.S.P.E.N.+position+paper:+Clinical+role+for+alternative+intravenous+fat+emulsions.">A.S.P.E.N. position paper: Clinical role for alternative intravenous fat emulsions.</a> Nutrition in Clinical Practice. 27 (2), 150-192 (2012).</li><li>Singer, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ESPEN+guidelines+on+parenteral+nutrition:+Intensive+care.">ESPEN guidelines on parenteral nutrition: Intensive care.</a> Clinical Nutrition. 28 (4), 387-400 (2009).</li><li>Calder, P. C., Jensen, G. L., Koletzko, B. V., Singer, P., Wanten, G. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lipid+emulsions+in+parenteral+nutrition+of+intensive+care+patients:+Current+thinking+and+future+directions.">Lipid emulsions in parenteral nutrition of intensive care patients: Current thinking and future directions.</a> Intensive Care Medicine. 36 (5), 735-749 (2010).</li><li>Umpierrez, G. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+double-blind,+randomized+clinical+trial+comparing+soybean+oil-based+versus+olive+oil-based+lipid+emulsions+in+adult+medical-surgical+intensive+care+unit+patients+requiring+parenteral+nutrition.">A double-blind, randomized clinical trial comparing soybean oil-based versus olive oil-based lipid emulsions in adult medical-surgical intensive care unit patients requiring parenteral nutrition.</a> Critical Care Medicine. 40 (6), 1792-1798 (2012).</li><li>Jia, Z. Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+and+efficacy+of+an+olive+oil-based+triple-chamber+bag+for+parenteral+nutrition:+A+prospective,+randomized,+multi-center+clinical+trial+in+China.">Safety and efficacy of an olive oil-based triple-chamber bag for parenteral nutrition: A prospective, randomized, multi-center clinical trial in China.</a> Nutrition Journal. 14, 119 (2015).</li><li>Tetzlaff, J. M., Moher, D., Chan, A. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Developing+a+guideline+for+clinical+trial+protocol+content:+Delphi+consensus+survey.">Developing a guideline for clinical trial protocol content: Delphi consensus survey.</a> Trials. 24 (13), 176 (2012).</li><li>Glasser, S. P., Howard, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+trial+design+issues:+At+least+10+things+you+should+look+for+in+clinical+trials.">Clinical trial design issues: At least 10 things you should look for in clinical trials.</a> Journal of Clinical Pharmacology. 46 (10), 1106-1115 (2006).</li><li>Ruikar, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interactive+voice/Web+response+system+in+clinical+research.">Interactive voice/Web response system in clinical research.</a> Perspectives in Clinical Research. 7 (1), 15-20 (2016).</li><li>Kulkarni, P. M., Meadows, E. S., Ahuja, S., Muram, D., Plouffe, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rationale+for+a+non-inferiority+clinical+trial+design+focused+on+subpopulations.">Rationale for a non-inferiority clinical trial design focused on subpopulations.</a> Current Medical Research and Opinion. 20 (10), 1641-1647 (2004).</li><li>Efird, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Blocked+randomization+with+randomly+selected+block+sizes.">Blocked randomization with randomly selected block sizes.</a> International Journal of Environmental Research and Public Health. 8 (1), 15-20 (2011).</li><li>Teitelbaum, D. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Proceedings+From+FDA/A.S.P.E.N.+Public+Workshop:+Clinical+Trial+Design+for+Intravenous+Fat+Emulsion+Products.">Proceedings From FDA/A.S.P.E.N. Public Workshop: Clinical Trial Design for Intravenous Fat Emulsion Products.</a> Journal of Parenteral and Enteral Nutrition. 39 (7), 768-786 (2015).</li><li>Pocock, S. J., Clayton, T. C., Stone, G. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Challenging+issues+in+clinical+trial+design:+Part+4+of+a+4-Part+series+on+statistics+for+clinical+trials.">Challenging issues in clinical trial design: Part 4 of a 4-Part series on statistics for clinical trials.</a> Journal of the American College of Cardiology. 66 (25), 2886-2898 (2015).</li></ol>

The randomized clinical trial protocol is a multi-purpose document. It not only provides guidance for the conduct of trial to the investigators, but it also makes ethics committees and institutional review boards aware of appropriate measures adopted to protect participants&#8217; safety and interests. A proper design is crucial for the success of a clinical trial. It is often noted that the design of a trial is connected with its successes/failures8.
Additionally, sele...

Parenteral nutrition is an essential component of overall therapy for a wide spectrum of indications, such as major gastrointestinal surgery, transient enteral intolerance, severe burns, coma; or for use in critically ill patients. Improvements in intravenous (IV) nutritional formulations and knowledge advancement regarding the implementation of therapy allow the safe and clinically efficacious administration of IV nutrition. These characteristics are particularly important in a metabolically stressed patient1.
Parenteral nutrition is commonly administered to patients by mixing nutrients that are compounded in the hospital pharmacy. Compounding total parenteral nutrition solutions from individual components is a multi-step, time-intensive process associated with a greater risk of human error. Recently, triple-chamber bag (3CB) systems have been developed in which individual components are separated by nonpermanent breakable seals. The contents of a 3CB include a glucose solution, an amino-acid solution, a lipid emulsion, with or without electrolytes. Prior to administration, the seal separating the various components of the 3CB is broken, enabling the components of the chambers to be admixed. The advantages offered by the 3CB includes increased physio-chemical shelf life of components, reduction the extent of contamination during preparation, and cutting down on the steps required in the preparation of a PN product2.
Lipid emulsion is an important ingredient in a PN formula; it can produce different clinical effects, depending upon the constituent fatty acids. Soybean-oil-based lipid emulsions primarily consist of long-chain linoleic acid (&#969;-6 polyunsaturated fatty acid [&#969;-6 PUFA]), which is mainly proinflammatory. Experimental data suggest that &#969;-6 PUFA-rich lipid emulsions may amplify the inflammatory response during stress and traumatic conditions, as well as increasing the infection rate3. On the other hand, olive-oil-based lipid emulsions, which consist of long-chain oleic acid (&#969;-9 monounsaturated fatty acids, [&#969;-9 MUFAs]), have a neutral response on the immune system3,4. Substituting soybean-oil-based &#969;-6 PUFAs with olive-oil-based &#969;-9 MUFAs can make the PN safe and further widen its clinical application5,6. However, there are limited clinical data in this connection.
Therefore, the present study aims to evaluate the rate of infections in two different lipid emulsions that varied in the content of linoleic acid, in addition to having the primary objective of assessing the safety and efficacy of 3CBs compared to CoBs for delivering PN. The assessment was carried out in adult hospitalized patients scheduled to undergo surgery for whom enteral nutrition was either not possible, inadequate, or inadvisable.

a clinical trial assessing the safety, efficacy, and delivery of olive-oil-based three-chamber bags for parenteral nutrition

Limited evidence exists to precisely estimate efficacy and safety differences between parenteral nutrition (PN) prepared using olive-oil-based three-chamber bags (3CBs) and soybean-oil-based compounded bags (CoBs) in hospitalized adult patients. We designed a multicenter, randomized, prospective, open-label, noninferiority protocol to compare the efficacy, safety, and distribution of olive-oil-based 3CBs and soybean-oil-based CoB formulations in adult Chinese patients requiring PN during surgical intervention. Subjects were randomized to receive either one of the study treatments using an interactive voice or web-based recognition system in accordance with the randomization code. Randomization was further stratified based on the study site and surgical category. Both treatment groups received similar amounts of calories and protein. In addition, the two study treatments contained a similar composition of the amino-acid component. The only difference between the two PN formulations was the lipid constitution. The duration of administration of study treatments was a minimum of 5 days up to a maximum of 14 days after the surgical procedure. The primary efficacy endpoint was serum prealbumin levels on day 5 of the study. Noninferiority was proved if the anti-log of the lower bound of the 95% confidence interval (CI) of the treatment difference was at least 0.80. Other efficacy measures included treatment preparation time; duration to achieve tolerability of oral nutrition; associated infectious complications; length of hospitalization; and laboratory assessment of markers of nutrition, inflammation, metabolism, and oxidative stress. A total of 458 patients were enrolled in the study. The results showed that olive-oil-based 3CBs were non-inferior to soybean-based CoBs, besides being well tolerated. The infection rate was found to be significantly lower in the olive-oil-based 3CB group. Thus, this study may be used as a reference for future research on lipid emulsion and 3CBs.

Patient Disposition 
Out of the 480 patients who gave their consent, a total of 458 patients were enrolled and randomized in the study. The ITT population included all randomized patients, of whom 226 constituted the test group and 232 the control group. The safety population included a total of 453 patients, of whom 222 belonged to the test group and 231 to the control group. The modified intention-to-treat (mITT) population comprised a total of 443 patients, of whom 219 were in the test group and ...

Watch this Scientific Journal Video about A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition at JoVE.com

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition

Here, we present a protocol for a study comparing the efficacy, safety, and delivery of olive-oil-based 3CB and soybean-oil-based CoB formulations in adults requiring parenteral nutrition. The results revealed that olive-oil-based 3CBs is non-inferior and well tolerated compared to soybean formulations.

Limited evidence exists to precisely estimate efficacy and safety differences between parenteral nutrition (PN) prepared using olive-oil-based ...

This protocol provided a template for future multiple centers, chambered chamber-bags. The protocol is consigned balance and efficacy, uh, clinical maneuverability so as to provide practical model for future research. This method could used as a reference for studies of parentaly administered and medical nutrition, especially for triple chamber-bags.The oddity is difficult to design and implement. Reference to a similar protocol maybe a shortcut for somebody who entered this field for the first time. Part of design implementation of this study can be clearly presented by text.To ensure a correct dosage for each of the treatments and keep the consistency of prescriptions, give each research site a table containing the exact PM composition of different weights. Administer the treatments to each participant through a peripheral intravenous catheter via a control pump. If an infusion is not possible or inadvisable via peripheral IV, infuse the study treatment via a peripherally inserted central catheter, or a central IV line.Gradually increase the flow rate during the first hour to 50 to 100 milliliters per hour and deliver the treatment for 12 to 22 hours for at least 5, and up to 14, days. On days 1 through 5, administer only the study treatment. To assess the primary efficacy outcome measure, of the serum pre-albumin level, on day 5, obtain 2 to 3 milliliter peripheral venous blood samples from a contralateral appendage from the peripheral IV study participant as well as at the time points indicated in the assessment schedule.Store the blood at 4 degrees celsius for up to 4 hours before transferring the samples to the central laboratory for analysis of the efficacy parameters. To assess the primary efficacy outcome measure of the urine output, collect urine for a 6 hour period on day 5, and according to the assessment schedule. Record the collected volume for the applicable treatment day before storing the sample at 4 degrees celsius.Then transfer an aliquot from the urine collection to the central laboratory for analysis of the efficacy parameters. For safety assessment of the treatment, survey the participant about any adverse or serious adverse events, and perform a vital sign assessment and physical examination. Then perform any other laboratory assessments according to the schedule.On day 6, and until the end of the study period, initiate the addition of liquid oral nutrition to the study treatment to meet the calculated daily nutrition requirements. Stop the study treatment once the subject receives at least 80 percent of the calculated daily nutrition requirements by the administered liquid oral nutrition or at the completion of the day 14 study treatment;whichever comes first. Upon completion or termination of the treatment, perform the appropriate end-of-treatment procedures for the participant according to the schedule.In this representative study, a total of 62 percent of patients underwent a high complexity surgery with a mean duration of 3 hours. A similar trend was also observed when the subgroup analysis for age"gender"no surgery"surgery of medium complexity"and surgery of high complexity"was performed for the 2 groups. The overall rate of infections was found to be low in the study, with the patients in the control group demonstrating a significantly higher infection rate compared to the test group.The most common infections observed in the study were lung infections, followed by incision and wound infections. The preparation time for the study treatment was also found to be significantly lower for the test group compared to the control group on all assessment days. First we should consider the clinical safety and the feasibility before study design.Another point, is that minimizes the difference around different sides is important that building protocol design for emerging center study.

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