Evidence map›Paper›PMID 33110039›Full record

Trial reportMenopause (New York, N.Y.)2020

TX-001HR is associated with a clinically meaningful effect on severity of moderate to severe vasomotor symptoms in the REPLENISH trial.

Ginger D Constantine, James A Simon, Andrew M Kaunitz, James H Pickar, Dennis A Revicki, Shelli Graham, Brian Bernick, Sebastian Mirkin

Registry-linked trialOpen access · hybridAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Menopause (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01942668 (A Phase 3 Study Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms in Postmenopausal Women With an Intact Uterus), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01942668 phase3completednot on this map

A Phase 3 Study Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms in Postmenopausal Women With an Intact Uterus

TypeinterventionalSponsorTherapeuticsMDRan2013 to 2016Enrolled1,845ConditionsMenopauseArmsEstradiol, Progesterone, Placebo
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Ginger D ConstantineEndoRheum Consultants, LLC, Malvern, PA.
James A SimonIntimMedicine Specialists, Washington, DC.
Andrew M KaunitzUniversity of Florida College of Medicine-Jacksonville, Jacksonville, FL.
James H PickarColumbia University Medical Center, New York, NY.
Dennis A RevickiPatient-Centered Research, Evidera, Bethesda, MD.
Shelli GrahamTherapeuticsMD, Boca Raton, FL.
Brian BernickTherapeuticsMD, Boca Raton, FL.
Sebastian MirkinTherapeuticsMD, Boca Raton, FL.
TherapeuticsMD (United States) · USFlorida College · USKing Mongkut's Institute of Technology Ladkrabang · TH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe aim of the study was to evaluate the clinically meaningful effect of oral TX-001HR (17β-estradiol [E2]/progesterone [P4]) capsules on hot flushes severity (vasomotor symptoms [VMS] severity scale) using the patient-reported Clinical Global Impression (CGI).

methodsREPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated TX-001HR in postmenopausal women (40-65 y) with a uterus. Those with frequent moderate to severe hot flushes (≥7/d or ≥50/wk) were randomized in a VMS substudy to daily E2/P4 (1/100, 0.5/100, 0.5/50, or 0.25/50 mg/mg), or placebo. Patients rated VMS severity from 1 (mild) to 3 (severe) and symptom improvements with the CGI. CGI results were an anchor in a nonparametric discriminant analysis to define clinically important differences (CIDs) and minimal CID in VMS severity at weeks 4 and 12.

resultsIn the VMS substudy (n = 726), determined CID and minimal CID severity thresholds were reductions of 0.525 and 0.350 points at week 4, respectively, and 0.775 and 0.225 points at week 12. Significantly more women taking the two highest E2/P4 doses (1/100 and 0.5/100) versus placebo met CID severity thresholds at weeks 4 (40% and 44% vs 17%; P < 0.05) and 12 (56% and 48% vs 29%; P < 0.05).

conclusionREPLENISH trial data demonstrated that E2/P4 1/100 and 0.5/100 provided clinically meaningful improvements in hot flushes severity in postmenopausal women. In conjunction with previously demonstrated clinically meaningful VMS frequency improvements, these data support oral E2/P4 1/100 and 0.5/100 for postmenopausal women with a uterus seeking treatment for moderate to severe VMS.

Indexed as

PostmenopauseProgesteroneDouble-Blind MethodEstradiolFemaleHot FlashesHumansTreatment OutcomeEstradiolProgesteroneTX-001HR

Identifiers

PMID33110039
PMCPMC7587237
OpenAlexW3042465175

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.