Emollient Therapy for Premature Infants in Zimbabwe

Very Low Birth Weight Infant Clinical Trial

Official title:

Emollient Therapy for Improved Survival and Growth of Very Low Birth Weight Infants in Zimbabwe

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05461404
• Other study ID #: 66546
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 1, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2023
• Source: Stanford University
• Contact: Gary Darmstadt, MD, MS
• Phone: 650-724-6014
• Email: gdarmsta[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy of topical emollient treatments in improving neonatal growth and mortality rates.

Description:

For infants whose parent/caretaker provides written informed consent, the study nurse coordinator on-site will allocate infants to one of two strata (700- <1000 g or 1000-1500 g). Participants within each stratum will be randomly assigned in a 1:1 ratio to one of two treatment groups: 1) high-linoleate SSO, or 2) standard-of-care treatment without use of topical emollients or massage.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 520
• Est. completion date: December 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 28 Days

Eligibility

Inclusion Criteria:

• infants <72 hours of age

• weigh 700-1500 at birth

• hospitalized at SMCH

Exclusion Criteria:

• infants who are moribund and highly likely not to survive despite any intervention

• significant breaches in their skin barrier

• conditions indicating failure to gain weight

• critically ill (definition below):

1. Oxygen saturation <88% on oxygen therapy AND =2 of the following conditions:

2. respiratory rate <20 or >100 breaths per minute

3. apnea requiring bag-mask ventilation

4. heart rate <100 or >200 beats per minute

• congenital syphilis

• hydrops fetalis

• a life-threatening congenital anomaly or major surgical condition requiring intervention

• generalized skin disease or a structural defect involving >5% body surface area likely to produce a defect in epidermal barrier function

Related Conditions & MeSH terms

• Birth Weight
• Very Low Birth Weight Infant

Intervention

Other:
• Topical Emollient Therapy
Application of high-linoleate (>60% linoleic acid) SSO to the epidermis.

Locations

Country	Name	City	State
Zimbabwe	Sally Mugabe Central Hospital (SMCH)	Harare

Sponsors (3)

Lead Sponsor	Collaborator
Stanford University	University of California, San Francisco, University of Zimbabwe

Country where clinical trial is conducted

Zimbabwe, 

References & Publications (12)

Cleminson J, McGuire W. Topical emollient for preventing infection in preterm infants. Cochrane Database Syst Rev. 2021 May 7;5(5):CD001150. doi: 10.1002/14651858.CD001150.pub4. — View Citation

Darmstadt GL, Badrawi N, Law PA, Ahmed S, Bashir M, Iskander I, Al Said D, El Kholy A, Husein MH, Alam A, Winch PJ, Gipson R, Santosham M. Topically applied sunflower seed oil prevents invasive bacterial infections in preterm infants in Egypt: a randomized, controlled clinical trial. Pediatr Infect Dis J. 2004 Aug;23(8):719-25. doi: 10.1097/01.inf.0000133047.50836.6f. — View Citation

Darmstadt GL, Mao-Qiang M, Chi E, Saha SK, Ziboh VA, Black RE, Santosham M, Elias PM. Impact of topical oils on the skin barrier: possible implications for neonatal health in developing countries. Acta Paediatr. 2002;91(5):546-54. doi: 10.1080/080352502753711678. — View Citation

Darmstadt GL, Saha SK, Ahmed AS, Ahmed S, Chowdhury MA, Law PA, Rosenberg RE, Black RE, Santosham M. Effect of skin barrier therapy on neonatal mortality rates in preterm infants in Bangladesh: a randomized, controlled, clinical trial. Pediatrics. 2008 Mar;121(3):522-9. doi: 10.1542/peds.2007-0213. — View Citation

Darmstadt GL, Saha SK, Ahmed AS, Chowdhury MA, Law PA, Ahmed S, Alam MA, Black RE, Santosham M. Effect of topical treatment with skin barrier-enhancing emollients on nosocomial infections in preterm infants in Bangladesh: a randomised controlled trial. Lancet. 2005 Mar 19-25;365(9464):1039-45. doi: 10.1016/S0140-6736(05)71140-5. — View Citation

Elias PM, Brown BE, Ziboh VA. The permeability barrier in essential fatty acid deficiency: evidence for a direct role for linoleic acid in barrier function. J Invest Dermatol. 1980 Apr;74(4):230-3. doi: 10.1111/1523-1747.ep12541775. — View Citation

Fischer N, Darmstadt GL, Shahunja KM, Crowther JM, Kendall L, Gibson RA, Ahmed T, Relman DA. Topical emollient therapy with sunflower seed oil alters the skin microbiota of young children with severe acute malnutrition in Bangladesh: A randomised, controlled study. J Glob Health. 2021 Jul 17;11:04047. doi: 10.7189/jogh.11.04047. eCollection 2021. — View Citation

Kumar A, Mishra S, Singh S, Ashraf S, Kan P, Ghosh AK, Kumar A, Krishna R, Stevenson DK, Tian L, Elias PM, Darmstadt GL, Kumar V; Shivgarh Emollient Research Group. Effect of sunflower seed oil emollient therapy on newborn infant survival in Uttar Pradesh, India: A community-based, cluster randomized, open-label controlled trial. PLoS Med. 2021 Sep 28;18(9):e1003680. doi: 10.1371/journal.pmed.1003680. eCollection 2021 Sep. — View Citation

Kumar V, Kumar A, Mishra S, Kan P, Ashraf S, Singh S, Blanks KJH, Baiocchi M, Limcaoco M, Ghosh AK, Kumar A, Krishna R, Stevenson DK, Tian L, Darmstadt GL; Shivgarh Emollient Research Group. Effects of emollient therapy with sunflower seed oil on neonatal growth and morbidity in Uttar Pradesh, India: a cluster-randomized, open-label, controlled trial. Am J Clin Nutr. 2022 Apr 1;115(4):1092-1104. doi: 10.1093/ajcn/nqab430. — View Citation

Prottey C, Hartop PJ, Black JG, McCormack JI. The repair of impaired epidermal barrier function in rats by the cutaneous application of linoleic acid. Br J Dermatol. 1976 Jan;94(1):13-21. doi: 10.1111/j.1365-2133.1976.tb04336.x. — View Citation

Salam RA, Darmstadt GL, Bhutta ZA. Effect of emollient therapy on clinical outcomes in preterm neonates in Pakistan: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2015 May;100(3):F210-5. doi: 10.1136/archdischild-2014-307157. Epub 2015 Jan 30. — View Citation

Salam RA, Das JK, Darmstadt GL, Bhutta ZA. Emollient therapy for preterm newborn infants--evidence from the developing world. BMC Public Health. 2013;13 Suppl 3(Suppl 3):S31. doi: 10.1186/1471-2458-13-S3-S31. Epub 2013 Dec 20. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Estimate a strata specific treatment effect, comparing mortality rates in infants 700- <1000 g or 1000-1500 g treated with SSO vs. control.	This aim will build upon methods used in the primary analysis. To estimate the change in mortality rate, and allowing the treatment effect to vary by strata, we will use a maximum likelihood approach, operationalized as a logistic model with fixed effects for study arm and strata, as well as an interaction term between study arm and strata.	Within 6 months of the end of enrollment
Other	Use residual inclusion modeling to isolate as much as possible the connection between weight gain and mortality.	For the exploratory analysis which aims to estimate the change in rate of mortality attributable to the change in weight, we will use an instrumental variable design. The study's randomization will be the "instrument," the "treatment" will be change in weight, and the "outcome" of interest will be mortality. This exploratory analysis will use a residual inclusion model approach to both testing and estimation, operationalized as a linear model in the first stage of the residual model and a logistic model in the second stage.	Within 6 months of the end of enrollment
Primary	Compare mortality rates for VLBW infants treated with SSO vs. control while hospitalized for up to 28 completed days	This will be an intent-to-treat analysis, using the randomization level rather than the received level of intervention.; To estimate the change in mortality rate, we will use a maximum likelihood approach, operationalized as a logistic model with fixed effects for study arm and strata random effects.	Baseline and 28 days
Secondary	Compare growth rates for VLBW infants treated with SSO vs. control while hospitalized for up to 28 completed days.	For the secondary analysis of change in growth rate, the quantity of interest is change in weight over the study period as a proportion of the infant's birthweight (g/kg/day). This secondary analysis will use a maximum likelihood approach to both testing and estimation, operationalized as a linear model with fixed effects for the study arm and strata.	Baseline and 28 days