Evidence map›Paper›PMID 35650639›Full record

Trial reportArthritis research & therapy2022

Zibotentan in systemic sclerosis-associated chronic kidney disease: a phase II randomised placebo-controlled trial.

Edward P Stern, Lauren V Host, Ivy Wanjiku, K Jane Escott, Peter S Gilmour, Rachel Ochiel, Robert Unwin, Aine Burns, Voon H Ong, Helen Cadiou and 2 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IILetterRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Arthritis research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02047708 (A Phase II, Single Centre, Randomised, Placebo-controlled, 3-part Trial to Assess the Safety, Tolerability and Efficacy of Zibotentan in Patients With Renal Disease Secondary to Scleroderma), which is not on this map. Cited by 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 pooled it
3.8field-weighted citation impact, top 6% 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.

NCT02047708 phase2completednot on this map

A Phase II, Single Centre, Randomised, Placebo-controlled, 3-part Trial to Assess the Safety, Tolerability and Efficacy of Zibotentan in Patients With Renal Disease Secondary to Scleroderma

TypeinterventionalSponsorUniversity College, LondonRan2014 to 2017Enrolled27ConditionsScleroderma, Scleroderma Renal Crisis, Chronic Kidney DiseaseArmsZibotentan
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Glomerular hyperfiltration as a therapeutic target for CKD.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Endothelin Receptor Antagonists in Kidney Disease.International journal of molecular sciences · 2023
    Review
  18. Review
  19. Review
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

12 authors at 4 institutions in 1 country.

Edward P SternDivision of Medicine, University College London, Royal Free Campus, London, UK.
Lauren V HostDivision of Medicine, University College London, Royal Free Campus, London, UK.
Ivy WanjikuDivision of Medicine, University College London, Royal Free Campus, London, UK.
K Jane EscottEmerging Innovations Unit, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Peter S GilmourEmerging Innovations Unit, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Rachel OchielDivision of Medicine, University College London, Royal Free Campus, London, UK.
Robert UnwinDivision of Medicine, University College London, Royal Free Campus, London, UK.
Aine BurnsDivision of Medicine, University College London, Royal Free Campus, London, UK.
Voon H OngDivision of Medicine, University College London, Royal Free Campus, London, UK.
Helen CadiouJoint Research Office, University College London, London, UK.
Aidan G O'KeeffeJoint Research Office, University College London, London, UK.
Christopher P DentonDivision of Medicine, University College London, Royal Free Campus, London, UK. c.denton@ucl.ac.uk.
The Royal Free Hospital · GBAstraZeneca (United Kingdom) · GBUniversity College London · GBUniversity of Nottingham · GB

Funding

Medical Research Council MR/K015230/1
6 · The paper itself

Abstract

backgroundWe report results from a phase II randomised placebo-controlled trial assessing zibotentan, a highly selective endothelin receptor antagonist (ERA), in chronic kidney disease (CKD) secondary to systemic sclerosis (SSc).

methodsThis trial included three sub-studies: ZEBRA 1-a randomised placebo-controlled, double-blind trial of zibotentan in SSc patients with CKD2 or CKD3 (and glomerular filtration rate (GFR) >45 ml/min) over 26 weeks; ZEBRA 2A-a 26-week placebo-controlled, single-blind trial of zibotentan in scleroderma renal crisis patients not requiring dialysis; and ZEBRA 2B-an open label pharmacokinetic study of zibotentan in patients on haemodialysis.

resultsSixteen patients were screened for ZEBRA 1. Of these, 6 patients were randomised to zibotentan and 7 to placebo. In ZEBRA 1, there were 47 non-serious adverse events (AE) during the trial. Twenty-seven occurred in the placebo group and 20 in the zibotentan group. One serious adverse event (SAE) occurred during ZEBRA1, in the placebo arm. Descriptive statistics did not suggest an effect of study drug on serum sVCAM1. Estimated GFR numerically declined in patients treated with placebo at 26 weeks and 52 weeks. In contrast, average eGFR increased in zibotentan-treated cases. The 4 patients in ZEBRA 2A experienced 8 non-serious AEs, distributed equally between placebo and zibotentan. There was one SAE each in placebo and zibotentan groups, both unrelated to study medication. ZEBRA 2B recruited 8 patients, 6 completed first dosing, and 2 completed a second dosing visit. Pharmacokinetic analysis confirmed zibotentan levels within the therapeutic range. Three patients experienced 3 non-serious AEs. One SAE occurred and was unrelated to study drug.

conclusionsZibotentan was generally well-tolerated. ZEBRA 1 did not show any effect of zibotentan on serum sVCAM-1 but was associated with numerical improvement in eGFR at 26 weeks that was more marked at 52 weeks. ZEBRA 2B suggested a feasible dose regimen for haemodialysis patients.

trial registrationEudraCT no: 2013-003200-39 (first posted January 28, 2014) ClinicalTrials.gov Identifier: NCT02047708 Sponsor protocol number: 13/0077.

Indexed as

Renal Insufficiency, ChronicScleroderma, SystemicHumansPyrrolidinesSingle-Blind MethodPyrrolidinesZD4054Chronic kidney diseaseEndothelinRenal crisisSclerodermaZibotentan

Identifiers

PMID35650639
PMCPMC9158153
OpenAlexW4281848047

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.