Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Zimbabwe | OTHER |
| University of California, San Francisco | OTHER |
Not provided
Not provided
Not provided
The purpose of this study is to assess the efficacy of topical emollient treatments in improving neonatal growth and mortality rates.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Topical Emollient Therapy | Other | Application of high-linoleate (>60% linoleic acid) SSO to the epidermis. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Inclusion Criteria:
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):
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
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gary Darmstadt, MD, MS | Contact | 650-724-6014 | gdarmsta@stanford.edu |
| Name | Affiliation | Role |
|---|---|---|
| Hilda A. Mujuru, MBChB, MMed, MSc | University of Zimbabwe | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sally Mugabe Central Hospital (SMCH) | Harare | Zimbabwe |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34386216 | Background | 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. | |
| 12113324 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
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.
Not provided
| Baseline and 28 days |
| 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. | 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 |
| 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. |
| 33961715 | 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. |
| 7373078 | 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. |
| 1252336 | 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. |
| 15295221 | 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. |
| 34982820 | 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. |
| 15781099 | 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. |
| 18310201 | 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. |
| 25637007 | 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. |
| 24564550 | 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. |
| 34582448 | 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. |
| 38493088 | Derived | 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. |