Emollient Therapy for Premature Infants in Zimbabwe

NCT05461404 | Unknown DMC

• 1 other identifier: 66546
• Study Type: interventional
• Target: 520
• Locations: 1 country
• Sites: 1

Brief Summary

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

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Compare growth rates for VLBW infants treated with SSO vs. control while hospitalized for up to 28 completed days.

  Baseline and 28 days

Other Outcomes (2)

• Estimate a strata specific treatment effect, comparing mortality rates in infants 700- <1000 g or 1000-1500 g treated with SSO vs. control.

  Within 6 months of the end of enrollment

• Use residual inclusion modeling to isolate as much as possible the connection between weight gain and mortality.

  Within 6 months of the end of enrollment

Study Arms (2)

Emollient arm

EXPERIMENTAL

Infants will receive gentle, hygienic whole-body massage by trained nurses (not parents or other family members) with 3g of SSO per kg of body weight - a dose sufficient to saturate the skin - three times daily for the first 14 days and twice daily thereafter during the duration of their stay in the hospital until death, discharge or through day 28 after birth.

Other: Topical Emollient Therapy

Control arm

NO INTERVENTION

Infants in the control group will receive the standard of care for infants in the neonatal care unit, which does not include use of topical emollients or massage (i.e., family members will not be allowed to apply skin care products to their infants), or other particular measures to prevent skin breakdown or to modulate skin barrier function.

Interventions

Topical Emollient Therapy OTHER

Application of high-linoleate (\>60% linoleic acid) SSO to the epidermis.

Emollient arm

Eligibility Criteria

• Age: Up to 28 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• infants \<72 hours of age
• weigh 700-1500 at birth
• hospitalized at SMCH

You may not qualify if:

• 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):
• Oxygen saturation \<88% on oxygen therapy AND ≥2 of the following conditions:
• respiratory rate \<20 or \>100 breaths per minute
• apnea requiring bag-mask ventilation
• 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

Sponsors & Collaborators

• Stanford University: lead
• University of Zimbabwe: collaborator
• University of California, San Francisco: collaborator

Study Sites (1)

Sally Mugabe Central Hospital (SMCH)

Harare, Zimbabwe

Location

Related Publications (13)

• 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.

  PMID: 34386216 BACKGROUND

• 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.

  PMID: 12113324 BACKGROUND

• 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.

  PMID: 33961715 BACKGROUND

• 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.

  PMID: 7373078 BACKGROUND

• 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.

  PMID: 1252336 BACKGROUND

• 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.

  PMID: 15295221 BACKGROUND

• 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.

  PMID: 34982820 BACKGROUND

• 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.

  PMID: 15781099 BACKGROUND

• 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.

  PMID: 18310201 BACKGROUND

• 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.

  PMID: 25637007 BACKGROUND

• 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.

  PMID: 24564550 BACKGROUND

• 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.

  PMID: 34582448 BACKGROUND

• Hui A, Chimhini G, Saungweme M, Kaisi D, Munetsi E, Mujuru HA, Darmstadt GL. Postnatal care and acceptability of emollient therapy in very low birthweight infants in Harare, Zimbabwe: a qualitative analysis. BMC Pediatr. 2024 Mar 16;24(1):187. doi: 10.1186/s12887-024-04661-x.

  PMID: 38493088 DERIVED

Study Officials

• Hilda A. Mujuru, MBChB, MMed, MSc

  University of Zimbabwe

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gary Darmstadt, MD, MS

CONTACT

650-724-6014; gdarmsta@stanford.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Due to the visible nature of the intervention, it is not possible to completely mask allocation; thus, the trial will be open-label. However, study physicians will not have access to patient randomization lists.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: July 13, 2022
• First Posted: July 18, 2022
• Study Start: August 1, 2023
• Primary Completion: May 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 19, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

ZI (1)