My Healthcare News & Research — May 7, 2026 · Double-Dose Ivermectin No Better for Severe Scabies: The GALE CRUSTED Trial in the New England Journal of Medicine

On May 7, 2026, the New England Journal of Medicine published a randomised trial of how much oral ivermectin to give people with severe scabies, the itchy skin disease caused by a burrowing mite. In 2019 its investigators had written that no randomised controlled trial had ever been carried out in severe scabies. A team from 33 hospital dermatology departments across France, led by Charlotte Bernigaud, Giao Do-Pham and Olivier Chosidow, gave 133 adults with profuse or crusted scabies either the standard dose of ivermectin (200 micrograms per kilogram of body weight) or double that dose (400 micrograms per kilogram), three times over two weeks, on top of permethrin cream and a daily moisturising cream. Doubling the dose did not cure more people: 75% were cured with the higher dose and 82% with the standard dose, a difference that was not statistically significant. The trial, known as GALE CRUSTED (“gale” is French for scabies), was paid for by the French Ministry of Health and the French Society of Dermatology.

This is a blinded randomised controlled trial, the study design that best separates the effect of a treatment from chance and from the expectations of patients and doctors. It compared two doses of the same drug, not ivermectin against no ivermectin, and every patient also received permethrin cream. Its question was whether the higher dose works better, and its answer was no. Severe scabies is uncommon in wealthy countries and hard to study: the trial took more than four years to recruit, and many of its patients were frail older adults in hospital. Before it, the authors write, “data from randomized clinical trials are lacking, and the probability of cure is uncertain.”

The full paper is behind a paywall. This report is based on the published abstract and its PubMed and Crossref records, the trial’s public registration, the investigators’ 2019 funding application to the French Society of Dermatology, and medical-press summaries of the paper, which agree with each other on the figures they report. Where a detail comes from a press summary rather than the paper itself, this report says so.

Table of Contents

  1. At a Glance
  2. What Was Done
  3. What Was Found, Number by Number
  4. How Scabies and Its Treatments Work
  5. From Japanese Soil to a Nobel Prize
  6. How It Fits With Earlier Research
  7. What It Cannot Show, and What Remains Unknown
  8. What Guidelines and Agencies Say
  9. Since Then: May to October 2026
  10. Sources and Primary Documents
  11. Key Research Papers
  12. Connections

At a Glance

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What Was Done

Who could join. The trial’s registration lists adults aged 18 or older with one of two severe forms of scabies. Crusted scabies was defined as thick, scaly skin (hyperkeratosis) in at least two places. Profuse scabies was defined as a spreading red, scaly rash on the neck, face or trunk without that thickening. The diagnosis had to be confirmed by a positive skin scraping under the microscope and/or by dermoscopy, a magnified skin examination that can show the mite or its traces. People were not eligible if they were pregnant or breastfeeding, could not tolerate one of the treatments, had taken ivermectin or albendazole in the previous seven days, or had liver enzyme levels above three times normal.

The two groups. Patients were assigned at random, half and half, to one of two doses of oral ivermectin, “to be taken with food”:

Everyone also had 5% permethrin cream applied head to toe on days 0 and 7 (the registration specifies skin, hair and genital area) and an emollient (moisturising) cream every day from day 0 to day 28. The registration lists the participants, the treating doctors, the investigators and the people judging the results as all unaware of which dose each patient received.

What counted as cure. The primary end point was strict and had two parts: no mites, eggs or mite droppings on microscope or dermoscope examination on both day 18 and day 21, and no active scabies lesions on physical examination on day 28.

How long it took. According to the registration, the first patient was enrolled on October 11, 2017 and the last data were collected on January 12, 2022. The investigators’ 2019 funding application to the French Society of Dermatology, a public document, set out the plan: 130 patients from 43 centres over 24 months, with the stated aim of showing that the 400 µg/kg dose plus permethrin “est plus efficace” (is more effective) than the standard dose plus permethrin. Fifteen months after the first patient, 49 had been enrolled; the team asked for an 18-month extension and opened more centres. The final paper reports 133 patients from 33 dermatology departments.

Who the patients were. Press summaries of the paper report a median age of 67, with about a third of patients over 80. Nearly 60% were in hospital and 42% had a neurological or cognitive impairment. 59% had profuse scabies alone, 5% crusted scabies alone, and 36% both.

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What Was Found, Number by Number

Reading the odds ratio. An odds ratio of 1 would mean the two doses cured equally. The figure of 0.64 points toward fewer cures with the higher dose, but the 95% confidence interval runs from 0.25 (much worse) to 1.67 (noticeably better). Because that range includes 1, the trial cannot say that either dose was better than the other. It can say that the hoped-for advantage of the higher dose did not appear. The authors conclude that, among adults, the 400 µg/kg dose plus permethrin “was not superior to the standard 200-µg-per-kilogram dose” plus permethrin in curing severe scabies.

A note on the percentages. 82% of 66 patients is 54 patients, but 75% of 66 is not a whole number. The 75% is therefore probably an estimate from a method that handles missing assessments (press summaries mention incomplete assessment data). This report gives the percentages as published and does not convert them into head counts.

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How Scabies and Its Treatments Work

The mite. Human scabies is caused by Sarcoptes scabiei var. hominis, a microscopic mite that burrows into the epidermis, the outer layer of the skin, penetrating its surface layer, the stratum corneum. Its eggs and droppings stay in the skin, which is why the trial looked for them as well as for live mites. The 2017 European guideline states that “patients’ main complaint is nocturnal itch” (see itching). A 2018 French review describes spread by “direct and prolonged skin-to-skin contact,” less often through contaminated clothing, and names nursing homes and other institutions among the main places where outbreaks happen.

Ordinary and severe scabies. In crusted scabies (also called Norwegian scabies), which mostly affects people with weakened immunity, the mites multiply far beyond the numbers seen in ordinary scabies. The World Health Organization describes “thousands or millions” of mites in thick, scaly crusts, a form that spreads easily and can be life-threatening. The 2017 European guideline notes that it “occurs in immunocompromised hosts and may be associated with reduced or absent pruritus,” meaning the person may hardly itch at all. In the largest published case series of crusted scabies, 78 patients in northern Australia, more than half had an identifiable cause of weakened immunity, 17% had a history of leprosy, and 42% had no identifiable risk factor. Profuse scabies, the other form included in this trial, is a widespread rash without the crusting.

Why it matters beyond the itch. Scratched skin lets bacteria in. A 2024 review in Nature Reviews Disease Primers lists secondary bacterial infections that “can cause severe health complications, including sepsis or necrotizing soft-tissue infection, renal damage and rheumatic heart disease.” The bacteria involved are mainly group A Streptococcus and Staphylococcus aureus.

How the two drugs act. Ivermectin and permethrin both attack the mite’s nervous system. Ivermectin belongs to the avermectin family, which acts on glutamate-gated chloride channels, a type of nerve-and-muscle channel found in invertebrates such as worms and mites; a 1994 study cloned the first such channel and showed it was sensitive to avermectins. A 2017 review notes that the drug’s mode of action is best described for these channels but “remains incomplete.” Permethrin acts on the mite’s nerve sodium channels. A 2022 review states that the two drugs kill “only the motile stages” and, because they “lack ovicidal activities, repeat treatments are required.” In other words, neither drug reliably kills eggs, so the schedule in this trial (ivermectin on days 0, 7 and 14, permethrin on days 0 and 7) is built to catch mites that hatch after each dose.

Why a higher dose seemed worth testing. The paper’s background states that ivermectin “at higher doses has been effective in the treatment of some parasitic diseases,” and the 2019 funding application described existing doses and schedules for severe scabies as “not standardised and possibly suboptimal.” A 2002 study in 68 healthy adults found no sign of nervous-system toxicity at doses up to ten times the standard 200 µg/kg, and found that taking ivermectin with food raised the amount absorbed (the area under the blood-concentration curve) 2.6-fold. The GALE CRUSTED protocol specified that the tablets be taken with food.

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From Japanese Soil to a Nobel Prize

Ivermectin traces back to a handful of soil. In his 2015 Nobel lecture, Satoshi Ōmura wrote that “Japanese soil was the origin of one of the most important drugs of the world: ivermectin.” The Nobel Assembly’s 2015 press release describes how Ōmura, a microbiologist, isolated new strains of Streptomyces bacteria from soil samples in Japan, cultured many thousands of them and selected about 50 of the most promising; one of these later turned out to be Streptomyces avermitilis. William C. Campbell, a parasite biologist working in the United States, acquired the cultures and showed that a component from one of them was “remarkably efficient against parasites in domestic and farm animals.” The active agent was purified and named avermectin, then chemically modified into ivermectin (22,23-dihydroavermectin B1a), introduced in a 1983 paper in Science titled “Ivermectin: a potent new antiparasitic agent.” The full story is told on the site’s page on the discovery of ivermectin.

A 2004 review co-written by Ōmura describes the drug as arising from “a unique international collaboration between the public and private sectors,” and its development as including “the world’s first and largest drug-donation programme,” through which ivermectin has been given free of charge in programmes against river blindness (onchocerciasis) and lymphatic filariasis. The site’s page on river blindness and global health covers that programme.

In 2015 the Nobel Prize in Physiology or Medicine was divided, one half jointly to Campbell and Ōmura “for their discoveries concerning a novel therapy against infections caused by roundworm parasites” and the other half to Tu Youyou for her discoveries concerning a therapy against malaria. Scabies is not a roundworm infection, but ivermectin also kills the scabies mite, and a 2018 French review of scabies treatment notes: “Ivermectin is the only oral drug available.” The prize is listed with every other laureate on the site’s Nobel Prize in Physiology or Medicine page.

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How It Fits With Earlier Research

No earlier trial of doses in severe scabies. As the 2019 funding application noted, no randomised controlled trial had been carried out in severe scabies before this one. A 2018 Cochrane review of permethrin and ivermectin found 15 trials with 1,896 participants, nearly all conducted in South Asia or North Africa. It reported that oral ivermectin at the standard 200 µg/kg dose may clear scabies slightly less often than permethrin cream after one week (illustrative clearance 43% vs 65%), with little or no difference by four weeks after one to three doses or applications (86% vs 93%; risk ratio 0.92, 95% CI 0.82 to 1.03). Most of the evidence was of low or moderate certainty. It added: “We found no studies comparing systemic ivermectin in different doses that assessed safety outcomes.”

Crusted scabies in practice. In the northern Australian case series of 78 patients (2005), deaths fell after doctors introduced a protocol of “multiple doses of ivermectin combined with topical scabicides and keratolytic therapy” (treatments that soften and remove the crusts). That was an observational before-and-after comparison, not a trial, but the combined approach it describes is the one GALE CRUSTED tested in two doses.

The companion French trial in ordinary scabies. The same French network ran a second trial in classic, non-severe scabies, published in The BMJ on January 6, 2026. In 289 households (1,075 people) at 28 French hospitals, each household received either oral ivermectin 200 µg/kg or 5% permethrin cream on days 0 and 10 (children under 15 kg received permethrin). Every member of the household was cured in 71.8% of households with ivermectin vs 88.5% with permethrin (a difference of −16.7 percentage points, 95% CI −26.3 to −7.1), and the authors report the “statistical superiority of 5% permethrin cream.” Skin side effects occurred in 11.9% and 15.6% of participants respectively. That trial compared the two drugs on their own in ordinary scabies; GALE CRUSTED combined them in severe scabies and compared two ivermectin doses, so the two answer different questions.

Mass treatment in communities. In Fiji, a 2015 trial in the same journal randomly assigned three island communities to standard care, mass permethrin or mass ivermectin. Among 2,051 participants, scabies prevalence fell from 32.1% to 1.9% after a year with mass ivermectin (a 94% relative reduction, 95% CI 83 to 100), compared with 41.7% to 15.8% with mass permethrin and 36.6% to 18.8% with standard care. Impetigo, the bacterial skin infection that often follows scabies, fell from 24.6% to 8.0% with ivermectin. Mild adverse events were more common with ivermectin (15.6% vs 6.8%). That trial measured a whole-community strategy, a different question from treating one severely affected patient.

Resistance. Two lines of research explain why doctors watch for treatment failure. In 2004, Australian researchers documented ivermectin resistance in mites from two patients with repeatedly returning crusted scabies who had received 30 and 58 doses over about four years. In 2023, a Vienna study found a mutation known to cause “knockdown” resistance to permethrin-type insecticides in 97.0% of 67 mites from 64 patients, most of whom had not responded to permethrin. The GALE CRUSTED authors, according to press summaries, note that permethrin resistance is low in France, where the trial was run.

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What It Cannot Show, and What Remains Unknown

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What Guidelines and Agencies Say

The paper itself. The abstract states that “a combination of standard-dose oral ivermectin and topical scabicides is recommended for treatment” of severe scabies, and that the higher dose was not superior to that standard.

The 2017 European guideline. The European guideline for the management of scabies, whose authors include Olivier Chosidow, the trial’s senior author, states that “crusted scabies therapy requires a topical scabicide and oral ivermectin,” and that mass treatment of populations with endemic disease “can be performed with a single dose of ivermectin (200 micrograms/kg of bodyweight).” The treatments it lists as recommended for scabies are permethrin 5% cream, oral ivermectin and benzyl benzoate 25% lotion.

The World Health Organization. The WHO’s scabies fact sheet states that “at least 200 million people worldwide suffer from scabies at any one time” and that “in 2017, scabies and other ectoparasites were included as Neglected Tropical Diseases (NTDs) by the WHO.” It describes oral ivermectin as highly effective and notes that mass drug administration “strategies have the potential to substantially reduce prevalence of scabies.” A 2017 analysis from the Global Burden of Disease study found the heaviest burden in tropical regions, with the greatest burden in children, adolescents and the elderly, the last group being the one most represented in GALE CRUSTED.

How the press reported it. Most coverage reported the result accurately as no benefit from the higher dose. One US trade headline called the higher dose “less effective” than the standard dose; the paper does not show that, because its confidence interval includes no difference. One Brazilian medical portal printed the higher-dose cure rate as 72%; the published abstract gives 75%.

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Since Then: May to October 2026

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Sources and Primary Documents

The paper’s identifiers were checked against PubMed and Crossref. Its abstract, the trial registration and the investigators’ funding application were read in full; the main text of the paper is paywalled and was not read. Figures not in the abstract come from the registration, the funding application or the press summaries listed below, as marked in the text.

  1. Bernigaud C, Do-Pham G, Guichard E, Beylot-Barry M, Goujon E, Isnard C, et al., Giraudeau B, Chosidow O (2026). Combined Oral Ivermectin and 5% Permethrin Cream to Treat Severe Scabies. New England Journal of Medicine 394(18):1814-1823. Published May 7, 2026. — doi:10.1056/NEJMoa2411721 · PubMed PMID: 42090793
  2. ClinicalTrials.gov. A Randomized Controlled Double-blind Trial Assessing the Efficacy of a 400µg/kg Ivermectin / 5% Permethrin / Emollient Cream Regimen in Patients With Crusted Scabies as Compared to a 200µg/kg Ivermectin / 5% Permethrin / Emollient Cream Regimen (GALECRUSTED). — NCT02841215
  3. Do-Pham G (2019). GALE CRUSTED: application to the French Society of Dermatology research call, dated March 14, 2019 (in French). — sfdermato.org PDF
  4. Sehgal R, Bhusal CK, Sehgal A; Abbal MA; Chosidow O, Bernigaud C, Do-Pham G (reply) (2026). Oral Ivermectin and 5% Permethrin Cream for Severe Scabies. New England Journal of Medicine 395(8):829-830. — doi:10.1056/NEJMc2607458 · PubMed PMID: 42617127
  5. World Health Organization. Scabies fact sheet, updated May 31, 2023. — who.int
  6. The Nobel Assembly at Karolinska Institutet. The Nobel Prize in Physiology or Medicine 2015, press release, October 5, 2015. NobelPrize.org. — nobelprize.org

Coverage: Hospital Healthcare Europe, May 28, 2026, “Higher-dose ivermectin offers no advantage over standard regimen for severe scabies, trial finds” (source of the baseline characteristics, serious adverse event counts and listed limitations); Managed Healthcare Executive, May 12, 2026 (source of the death counts); Afya (source of the skin-reaction count); Alomedika (source of the by-group baseline figures).

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Key Research Papers

Background papers on scabies, its treatment and the history of ivermectin, in the order they appear above. Each entry was checked against its PubMed record before it was written down.

  1. Bernigaud C, Chosidow O (2018). [Scabies]. La Revue du Praticien 68(1):63-69. — PubMed PMID: 30840392
  2. Nardoni S, Mancianti F (2022). Essential Oils against Sarcoptes scabiei. Molecules 27(24):9067. — PubMed PMID: 36558200
  3. Roberts LJ, Huffam SE, Walton SF, Currie BJ (2005). Crusted scabies: clinical and immunological findings in seventy-eight patients and a review of the literature. Journal of Infection 50(5):375-381. — PubMed PMID: 15907543
  4. Fernando DD, Mounsey KE, Bernigaud C, Surve N, Estrada Chávez GE, Hay RJ, et al. (2024). Scabies. Nature Reviews Disease Primers 10(1):74. — PubMed PMID: 39362885
  5. Cully DF, Vassilatis DK, Liu KK, Paress PS, Van der Ploeg LH, Schaeffer JM, et al. (1994). Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 371(6499):707-711. — PubMed PMID: 7935817
  6. Laing R, Gillan V, Devaney E (2017). Ivermectin – Old Drug, New Tricks? Trends in Parasitology 33(6):463-472. — PubMed PMID: 28285851
  7. Fernando DD, Fischer K (2022). Spinosad topical suspension (0.9%): a new topical treatment for scabies. Expert Review of Anti-infective Therapy 20(9):1149-1154. — PubMed PMID: 35799317
  8. Guzzo CA, Furtek CI, Porras AG, Chen C, Tipping R, Clineschmidt CM, et al. (2002). Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects. Journal of Clinical Pharmacology 42(10):1122-1133. — PubMed PMID: 12362927
  9. Ōmura S (2016). A Splendid Gift from the Earth: The Origins and Impact of the Avermectins (Nobel Lecture). Angewandte Chemie International Edition 55(35):10190-10209. — PubMed PMID: 27435664
  10. Campbell WC, Fisher MH, Stapley EO, Albers-Schönberg G, Jacob TA (1983). Ivermectin: a potent new antiparasitic agent. Science 221(4613):823-828. — PubMed PMID: 6308762
  11. Ōmura S, Crump A (2004). The life and times of ivermectin – a success story. Nature Reviews Microbiology 2(12):984-989. — PubMed PMID: 15550944
  12. Rosumeck S, Nast A, Dressler C (2018). Ivermectin and permethrin for treating scabies. Cochrane Database of Systematic Reviews 4:CD012994. — PubMed PMID: 29608022
  13. Boralevi F, Simon G, Bernigaud C, Brun J, Goujon E, Perrot JL, et al., Giraudeau B, Chosidow O (2026). Oral ivermectin versus 5% permethrin cream to treat children and adults with classic scabies: multicentre, assessor blinded, cluster randomised clinical trial. BMJ 392:e086277. — PubMed PMID: 41494769
  14. Romani L, Whitfeld MJ, Koroivueta J, Kama M, Wand H, Tikoduadua L, et al. (2015). Mass Drug Administration for Scabies Control in a Population with Endemic Disease. New England Journal of Medicine 373(24):2305-2313. — PubMed PMID: 26650152
  15. Currie BJ, Harumal P, McKinnon M, Walton SF (2004). First documentation of in vivo and in vitro ivermectin resistance in Sarcoptes scabiei. Clinical Infectious Diseases 39(1):e8-e12. — PubMed PMID: 15206075
  16. Riebenbauer K, Purkhauser K, Walochnik J, Urban N, Weber PB, Stamm T, et al. (2023). Detection of a knockdown mutation in the voltage-sensitive sodium channel associated with permethrin tolerance in Sarcoptes scabiei var. hominis mites. Journal of the European Academy of Dermatology and Venereology 37(11):2355-2361. — PubMed PMID: 37356045
  17. Salavastru CM, Chosidow O, Boffa MJ, Janier M, Tiplica GS (2017). European guideline for the management of scabies. Journal of the European Academy of Dermatology and Venereology 31(8):1248-1253. — PubMed PMID: 28639722
  18. Karimkhani C, Colombara DV, Drucker AM, Norton SA, Hay R, Engelman D, et al. (2017). The global burden of scabies: a cross-sectional analysis from the Global Burden of Disease Study 2015. Lancet Infectious Diseases 17(12):1247-1254. — PubMed PMID: 28941561

PubMed Topic Searches

  1. PubMed: Ivermectin and crusted scabies
  2. PubMed: Ivermectin vs permethrin, randomised trials
  3. PubMed: Scabies mass drug administration
  4. PubMed: Drug resistance in the scabies mite

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Connections

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