George Uchenna Eleje,1,2 Henrietta Aritetsoma Ogbunugafor,1,3 Chiemelu Dickson Emegoakor,1,4 Ebere Innocent Okoye,1,5 Ogochukwu Ifeanyi Ezejiofor,6 Shirley Nneka Chukwurah,7 Joseph Ifeanyichukwu Ikechebelu,1,2 Godwin W Nchinda,8 Chidozie Godwin Ugochukwu,3 Lucy Ijeoma Nnaji-Ihedinmah,9 Festus Basden C Okoye,1,10 Frank Uchenna Eneh,3 Michael Emeka Onwukamuche,11 Charles Okechukwu Esimone1,12 1Biomedicine Research Group, Nnamdi Azikiwe University, Awka, Nigeria; 2Effective Care Research Unit, Faculty of Medicine, College of Health Sciences, Nnamdi Azikiwe University, Awka, Nigeria; 3Department of Applied Biochemistry, Nnamdi Azikiwe University, Awka, Nigeria; 4Department of General Surgery, Nnamdi Azikiwe University, Awka, Nigeria; 5Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Nigeria; 6Department of Medicine, Nnamdi Azikiwe University, Awka, Nigeria; 7Gastroenterology Unit, Department of Medicine, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria; 8Laboratory of Vaccinology/Biobanking, CIRCB BP 3077, Messa Yaounde, Cameroon; 9Department of Chemical Pathology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria; 10Department of Pharmaceutical and Medicinal Chemistry, Nnamdi Azikiwe University, Awka, Nigeria; 11Department of Histopathology, Faculty of Medicine, Nnamdi Azikiwe University, Awka, Nigeria; 12Department of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe University, Awka, Nigeria Background: To our knowledge, there is no prior randomized study on the utility of Syferol-IHP (blend of virgin coconut oil and Ocimum sanctum oil) when coadministered with a triple therapy schedule.Aim: This study determined the efficacy and safety of Syferol-IHP as adjunct to conventional triple therapy for the treatment of peptic ulcer disease (PUD).Methods: A pilot double-blind randomized trial was conducted in patients with confirmed diagnosis (endoscopy-guided biopsy) of PUD. Eligible patients were randomized to Pylorest (a three-in-one tablet containing rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg) and Syferol-IHP for 2 weeks, followed by rabeprazole and Syferol-IHP for 2 weeks or Pylorest and placebo for 2 weeks, followed by rabeprazole and placebo for 2 weeks. Repeat endoscopy-guided biopsy and histology were done 4 weeks posttherapy. Primary outcome measures were the healing of ulcer and eradication of Helicobacter pylori. Secondary outcome measures were the disappearance of epigastric pain, gastritis, and duodenitis. Analysis was by intention-to-treat.Results: Of the 63 patients enrolled, 60 patients had complete evaluation, with 37 patients receiving Pylorest and Syferol-IHP and 23 patients receiving Pylorest and Placebo. Healing of the PUD in favor of Pylorest and Syferol-IHP was significantly higher for gastric ulcer (RR=0.000, 95% CI=undefined, P=0.048) but not for duodenal ulcer (RR=0.400, 95% CI=0.07–2.37, P=0.241). H. pylori eradication was 100% with Syferol-IHP vs 50% with placebo (P=0.066). Epigastric pain (reduction to 16.2% vs 43.5%; P=0.021), gastritis (reduction to 13.5% vs 39.1%; P=0.024), and duodenitis (reduction to 0% vs 8.7%; P=0.327) were observed in the Syferol-IHP and Pylorest vs placebo and Pylorest groups, respectively. Adverse events (RR=0.971, 95% CI=0.46–2.04, P=0.937) and laboratory parameters were not significantly different pre- and posttherapies (P>0.05, for both groups).Conclusion: Although both treatment arms were equally safe, co-administration of Syferol-IHP and triple therapy is more efficacious than triple therapy alone for treating PUD. Pan African Clinical trial registry identifier number is PACTR201606001665364. Keywords: gastritis, duodenitis, virgin coconut oil, Ocimum sanctum oil, triple therapy, Pylorest, gastric ulce