The trials that changed practice: olanzapine, and the repellent that reached Geneva

2016 · 2025 · BOUNDARY — IUSM–SOUTH BEND / NOTRE DAME · ROW 8

Two practice-changing trials carry investigators seated at this ground's boundary campuses; a sweep for a trial seated in the CDP itself returns none, and that negative prints with the pair: no clinical trial in the PubMed or ClinicalTrials.gov record reached carries a Granger-CDP affiliation — the ground has no hospital, no school, and no research institute at which a trial could seat — and the Parseghian foundation's Niemann-Pick Type C work, carried in the people file, is research funding and advocacy, not a trial. The course this ground's patients actually entered runs through South Bend, twice over.

The nausea trial. Rudolph M. Navari of the Indiana University School of Medicine–South Bend led the randomized, double-blind, phase 3 trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting, published in the New England Journal of Medicine on 14 July 2016 (375:134–142; ClinicalTrials.gov NCT02116530; funded by the National Cancer Institute). Three hundred eighty chemotherapy-naïve patients receiving highly emetogenic chemotherapy — cisplatin or cyclophosphamide-doxorubicin — were randomized to olanzapine or placebo, each added to dexamethasone, an NK1-receptor antagonist, and a 5-HT3-receptor antagonist. The proportion with no nausea was 74% against 45% in the first 24 hours, 42% against 25% across 25–120 hours, and 37% against 22% overall (P=0.002 at each window), with the complete-response rate likewise improved. The trial's distinction, in its lead author's own contemporary account, is that it was the first study to take nausea itself — not vomiting alone — as the primary endpoint, and its result entered antiemetic guidelines: an inexpensive, already-approved antipsychotic became a standard fourth drug in the prophylaxis of the most emetogenic regimens. The investigator's seat is the boundary campus of Row 3; the trial's patients were enrolled through the national NCORP network, this county's among them by the network's design, though site-level enrollment for St. Joseph County is not separated in the record reached and is not claimed.

The repellent course. The second trial line is a vector-control course run from Notre Dame's Eck Institute for Global Health: the AEGIS project — Advancing Evidence for the Global Implementation of Spatial Repellents — led by the University of Notre Dame and funded by Unitaid, with Nicole L. Achee as lead principal investigator and scientific director and John P. Grieco among its senior investigators. In the AEGIS cluster-randomized trial in Kenya (with the Kenya Medical Research Institute and the U.S. Centers for Disease Control and Prevention), first-time malaria infections ran one-third lower in homes using spatial repellents together with insecticide-treated nets than in homes with nets and a placebo emanator; the Kenya findings were published in The Lancet. On 13 August 2025 the World Health Organization issued a conditional recommendation for spatial emanators — spatial repellents — alongside insecticide-treated nets in its malaria guidelines, with prequalification of two products; Unitaid's announcement calls them the first new malaria vector-control tool recommended in decades, and states that the recommendation is largely based on the Notre Dame-led AEGIS evidence. The course prints whole, including its limit: the parallel AEGIS trial in Mali (medRxiv, August 2025, not peer-reviewed at posting) did not demonstrate efficacy, and the WHO recommendation is expressly conditional. A trial program that ends in a dated WHO recommendation, with its negative sibling trial in print, is the strongest form of "changed practice" this county's research record holds — and, like the nausea trial, it is seated at Notre Dame / South Bend, at boundary size, in its home institutions' names.

Sources:

1. Navari RM et al., "Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting," New England Journal of Medicine 375(2):134–142 (14 July 2016), PubMed 27410922 — affiliation "Indiana University School of Medicine–South Bend (R.M.N.)"; NCT02116530; the nausea and complete-response figures as printed.
2. Contemporary trial accounts (Medscape Medical News; Cancer Therapy Advisor, 2015–2016) — the first nausea-primary-endpoint design, in the lead author's account; "practice-changing," in his assessment.
3. University of Notre Dame Research news (30 September 2025) and Unitaid announcement (13 August 2025) — the WHO conditional recommendation for spatial emanators; the AEGIS Kenya trial, The Lancet; one-third fewer first-time infections; Achee as lead PI; prequalification of Mosquito Shield and Guardian.
4. Sagara I. et al., "Effect of a spatial repellent on malaria incidence in Mali: a cluster-randomized, controlled trial," medRxiv (posted 6 August 2025) — the Mali AEGIS trial's null result, printed as the course's limit.