NIT_CH: A study protocol for evaluating the effect of inorganic nitrate capsules in chronic hypertensive pregnancies - a triple-blind placebo-controlled randomized trial.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) represent a substantial risk to maternal and fetal health, with increasing prevalence worldwide linked to factors such as advanced maternal age, rising obesity rates, and metabolic syndrome. Effective management of borderline hypertension during pregnancy remains critical. However, given the limited safety data on conventional antihypertensive drugs in this population, alternative therapeutic strategies are needed. Inorganic nitrate supplementation has demonstrated potential in reducing blood pressure and enhancing maternal uterine artery function, primarily due to the production of nitric oxide (NO) from nitrate. We will evaluate whether early initiation and sustained supplementation with inorganic nitrate capsules can control blood pressure and improve maternal and perinatal outcomes in women with chronic hypertension during pregnancy. METHODS: This randomized, triple-blind, placebo-controlled clinical trial intends to recruit an estimated sample size of 144 pregnant women with chronic hypertension. Once included, participants will receive standard antihypertensive treatment and preeclampsia prophylaxis and will be randomized into either the treatment or placebo group. Starting from the 16th week and continuing until delivery, patients will undergo continuous monitoring of blood pressure, maternal and fetal ultrasonography, as well as biochemical and dietary assessments. The primary aim of the study is to evaluate blood pressure control. At the same time, secondary objectives include monitoring the need for additional antihypertensive medications, the occurrence of preeclampsia and fetal growth restriction, Doppler parameters, biochemical and inflammatory markers profiles, and perinatal outcomes. Data analyses will be conducted using both R and Stata software tools for descriptive and analytic statistics, with a significance level of p < 0.05. DISCUSSION: Evaluating the efficacy of inorganic nitrate as an adjunctive treatment for chronic hypertension during pregnancy could provide an alternative to conventional antihypertensive therapies. Successful results may offer a safer and natural option to help manage blood pressure, improve outcomes for both mothers and infants, and potentially guide the development of new strategies for managing hypertensive disorders in pregnant patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT06105775 (Registration Date: October 27, 2023 – updated on March 26, 2025).