Efficacy of Nafamostat in Covid-19 Patients (RACONA Study)

NCT04352400 | Unknown Phase 2 DMC

• 1 other identifier: RACONA Nafamostat
• Study Type: interventional
• Target: 256
• Locations: 1 country
• Sites: 1

Brief Summary

RACONA is a prospective trial that will test the hypothesis that nafamostat can lower lung function deterioration and need for intensive care admission in COVID-19 patients. Design: Adult hospitalized COVID-19 patients will be randomized in a prospective double-blind randomized placebo-controlled study to test the clinical efficacy of nafamostat mesylate (administered intravenously) on top of best standard of care. Primary outcome measures: the time-to-clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven category ordinal scale or live discharge from the hospital, whichever comes first.

Conditions

COVID19

Keywords

Nafamostat; proteases; TMPRSS2; covid-19; coronavirus

Outcome Measures

Primary Outcomes (1)

• Time-to-clinical improvement

  Time-to-clinical improvement (time from randomization to an improvement of two points (from the status at randomization) on a 7 category ordinal scale or live discharge from the hospital, whichever came first.

  day 1 until day 28

Secondary Outcomes (8)

• Responders

  day 1 until day 28

• Critical or dead patients

  day 1 until day 28

• pO2/FiO2 ratio

  day 1 until day 28

• SOFA score over time

  day 1 until day 28

• Hospitalization

  day 1 until day 28

Study Arms (2)

Nafamostat

ACTIVE COMPARATOR

Nafamostat mesylate on top of best standard of care.

Drug: Nafamostat Mesilate

Placebo

PLACEBO COMPARATOR

Placebo on top of best standard of care.

Drug: Placebo

Interventions

Nafamostat Mesilate DRUG

administered intravenously as a continuous infusion

Also known as: no alternative name. Commercial brands are available.

Nafamostat

Placebo DRUG

administered intravenously as a continuous infusion

Also known as: no alternative name.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalized, COVID-19 positive, between 18 and ≤ 85 years of age;
• Signed Inform Consent Form;
• Body temperature \> 37.3 ℃;
• Oxygenation criterion (any of the following): i) Oxygen saturation ≤94% on Room Air; ii) PaO2/FiO2 ratio ≤300 mmHg but \> 100 mmHg, if patient on supplemental oxygen; iii) SpO2/FiO2\<200 if no arterial blood gas available;
• Respiratory rate (RR) ≥ 25 beats/min.

You may not qualify if:

• Pregnant or lactating females;
• Unwillingness or inability to complete the study.
• Rapidly deteriorating clinical condition or low likelihood to complete the study according to the investigator;
• eGFR \< 30 ml/min/m2 assessed with CKD EPI formula;
• Current or chronic history of liver disease (Child Pugh score ≥ 10), or known hepatic or biliary abnormalities;
• Participation in a clinical trial with an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer);
• Patients requiring high doses of loop diuretics (i.e. \> 240 mg furosemide daily) with significant intravascular volume depletion, as assessed clinically;
• History of allergy;
• History of sensitivity to heparin or heparin-induced thrombocytopenia;
• Unstable hemodynamics in the preceding 4 hours (SBP \< 90 mmHg, and/or vasoactive agents required);
• Hemoglobin \< 7 at time of drug infusion. Transfusion is allowed to increase hemoglobin levels before entry into the study;
• Malignancy or any other condition for which estimated 6-month mortality \>50%;
• Arterial blood pH less than 7.2;
• Known evidence of chronic interstitial infiltration at imaging;
• Known hospitalization within the past six months for respiratory failure (PaCO2 \> 50 mmHg or PaO2 \< 55 mmHg, or oxygen saturation \<88% on FiO2 = 0.21);

Sponsors & Collaborators

• University Hospital Padova: lead
• Yokohama City University: collaborator
• University of Zurich: collaborator

Study Sites (1)

Azienda Ospedale Università di Padova

Padua, 35128, Italy

RECRUITING

Related Publications (9)

• Yamamoto M, Matsuyama S, Li X, Takeda M, Kawaguchi Y, Inoue JI, Matsuda Z. Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6532-6539. doi: 10.1128/AAC.01043-16. Print 2016 Nov.

  PMID: 27550352 RESULT

• Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5.

  PMID: 32142651 RESULT

• Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

  PMID: 32171076 RESULT

• Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18.

  PMID: 32187464 RESULT

• Minakata D, Fujiwara SI, Ikeda T, Kawaguchi SI, Toda Y, Ito S, Ochi SI, Nagayama T, Mashima K, Umino K, Nakano H, Yamasaki R, Morita K, Kawasaki Y, Sugimoto M, Yamamoto C, Ashizawa M, Hatano K, Sato K, Oh I, Ohmine K, Muroi K, Ohmori T, Kanda Y. Comparison of gabexate mesilate and nafamostat mesilate for disseminated intravascular coagulation associated with hematological malignancies. Int J Hematol. 2019 Feb;109(2):141-146. doi: 10.1007/s12185-018-02567-w. Epub 2018 Dec 8.

  PMID: 30536180 RESULT

• Yu G, Li S, Wan R, Wang X, Hu G. Nafamostat mesilate for prevention of post-ERCP pancreatitis: a meta-analysis of prospective, randomized, controlled trials. Pancreas. 2015 May;44(4):561-9. doi: 10.1097/MPA.0000000000000310.

  PMID: 25822153 RESULT

• Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001 Oct 10;286(14):1754-8. doi: 10.1001/jama.286.14.1754.

  PMID: 11594901 RESULT

• Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

  PMID: 35244208 DERIVED

• Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.

  PMID: 33502773 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

nafamostat

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Gian Paolo Rossi, Prof.

  University of Padova, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gian Paolo Rossi, Prof.

CONTACT

0039049821; gianpaolo.rossi@unipd.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization will be done with an algorithm tailored to the study design. Investigators and patients will be blinded to the treatment administered.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: Randomized, double blind, placebo-controlled parallel-group trial, on top of best standard of care

Study Record Dates

• First Submitted: April 3, 2020
• First Posted: April 20, 2020
• Study Start: June 4, 2021
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)