Clinical trial NCT05461404: Emollient Therapy for Premature Infants in Zimbabwe
Official title: Emollient Therapy for Improved Survival and Growth of Very Low Birth Weight Infants in Zimbabwe
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Very Low Birth Weight Infant
Keywords: emollient therapy
sunflower seed oil (SSO)
skin barrier
Zimbabwe
neonatal mortality
newborn care
preterm infants
postnatal care
growth
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: University of Zimbabwe
name: University of California, San Francisco
First posted: 2022-07-18
Enrollment: 520
Sex: ALL
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Infants will be enrolled after informed consent, stratified by birthweight (700- \<1000 g, 1000-1500 g) and randomly allocated 1:1 to the two arms of the trial which will be run in parallel.
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Compare mortality rates for VLBW infants treated with SSO vs. control while hospitalized for up to 28 completed days
timeFrame: Baseline and 28 days
Secondary outcomes:
measure: Compare growth rates for VLBW infants treated with SSO vs. control while hospitalized for up to 28 completed days.
timeFrame: Baseline and 28 days
Other outcomes:
measure: Estimate a strata specific treatment effect, comparing mortality rates in infants 700- <1000 g or 1000-1500 g treated with SSO vs. control.
timeFrame: Within 6 months of the end of enrollment
measure: Use residual inclusion modeling to isolate as much as possible the connection between weight gain and mortality.
timeFrame: Within 6 months of the end of enrollment
Locations:
city: Harare
country: Zimbabwe
facility: Sally Mugabe Central Hospital (SMCH)
Study officials:
affiliation: University of Zimbabwe
name: Hilda A. Mujuru, MBChB, MMed, MSc
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.