A description of the methods of the aspirin supplementation for pregnancy indicated risk reduction in nulliparas (ASPIRIN) study

Matthew K Hoffman, Shivaprasad S Goudar, Bhalachandra S Kodkany, Norman Goco, Marion Koso-Thomas, Menachem Miodovnik, Elizabeth M McClure, Dennis D Wallace, Jennifer J Hemingway-Foday, Antoinette Tshefu, Adrien Lokangaka, Carl L Bose, Elwyn Chomba, Musaku Mwenechanya, Waldemar A Carlo, Ana Garces, Nancy F Krebs, K Michael Hambidge, Sarah Saleem, Robert L Goldenberg, Archana Patel, Patricia L Hibberd, Fabian Esamai, Edward A Liechty, Robert Silver, Richard J Derman, Matthew K Hoffman, Shivaprasad S Goudar, Bhalachandra S Kodkany, Norman Goco, Marion Koso-Thomas, Menachem Miodovnik, Elizabeth M McClure, Dennis D Wallace, Jennifer J Hemingway-Foday, Antoinette Tshefu, Adrien Lokangaka, Carl L Bose, Elwyn Chomba, Musaku Mwenechanya, Waldemar A Carlo, Ana Garces, Nancy F Krebs, K Michael Hambidge, Sarah Saleem, Robert L Goldenberg, Archana Patel, Patricia L Hibberd, Fabian Esamai, Edward A Liechty, Robert Silver, Richard J Derman

Abstract

Background: Preterm birth (PTB) remains the leading cause of neonatal mortality and long term disability throughout the world. Though complex in its origins, a growing body of evidence suggests that first trimester administration of low dose aspirin (LDA) may substantially reduce the rate of PTB.

Methods: Hypothesis: LDA initiated in the first trimester reduces the risk of preterm birth. Study Design Type: Prospective randomized, placebo-controlled, double-blinded multi-national clinical trial conducted in seven low and middle income countries. Trial will be individually randomized with one-to-one ratio (intervention/control) Population: Nulliparous women between the ages of 14 and 40, with a singleton pregnancy between 6 0/7 weeks and 13 6/7 weeks gestational age (GA) confirmed by ultrasound prior to enrollment, no more than two previous first trimester pregnancy losses, and no contraindications to aspirin.

Intervention: Daily administration of low dose (81 mg) aspirin, initiated between 6 0/7 weeks and 13 6/7 weeks GA and continued to 36 0/7 weeks GA, compared to an identical appearing placebo. Compliance and outcomes will be assessed biweekly.

Outcomes: Primary outcome: Incidence of PTB (birth prior to 37 0/7 weeks GA). Secondary outcomes Incidence of preeclampsia/eclampsia, small for gestational age and perinatal mortality.

Discussion: This study is unique as it will examine the impact of LDA early in pregnancy in low-middle income countries with preterm birth as a primary outcome. The importance of developing low-cost, high impact interventions in low-middle income countries is magnified as they are often unable to bear the financial costs of treating illness.

Trial registration: ClinicalTrials.gov identifier: NCT02409680 Date: March 30, 2015.

Keywords: Low dose Aspirin; Prematurity; Preterm birth.

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