| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Complicated Intra-Abdominal Infection (cIAI) |
| Croatian: Komplicirana intraabdominalna infekcija (cIAI) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Abdominal infection |
| Croatian: Abdominalna infekcija |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10056570 |
| E.1.2 | Term | Intra-abdominal infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the noninferiority of ceftazidime avibactam (CAZ104) plus metronidazole compared to meropenem alone with respect to clinical cure at the test-of-cure in patients who have at least 1 identified pathogen. |
| Croatian: Procijeniti neinferiornost ceftazidim-avibaktama (CAZ-AVI) u kombinaciji s metronidazolom u usporedbi s meropenemom prema kliničkoj izliječenosti u trenutku posjeta za utvrđivanje izlječenja u ispitanika koji su imali barem 1 identificirani patogen. |
|
| E.2.2 | Secondary objectives of the trial |
To determine the efficacy of CAZ104 plus metronidazole compared to meropenem with respect to the clinical cure at the end of treatment with IV therapy (EOT) and at the late follow-up (LFU)
To determine the per-patient and per-pathogen microbiologic response of CAZ104 plus metronidazole compared to meropenem at EOT, TOC, and LFU
To evaluate the efficacy of CAZ104 plus metronidazole versus meropenem in
pathogens resistant to ceftazidime
To compare the time to first defervescence of CAZ104 plus metronidazole versus
meropenem
To evaluate the safety and tolerability profile of CAZ104 plus metronidazole
compared to meropenem
|
Croatian:
• Utvrditi učinkovitost ceftazidim-avibaktama u kombinaciji s metronidazolom u usporedbi s meropenemom prema kliničkoj izliječenosti u trenutku posjeta za utvrđivanje izliječenosti u ispitanika koji su mikrobiološki procjenjivi.
• Utvrditi učinkovitost ceftazidim-avibaktama u kombinaciji s metronidazolom u usporedbi s meropenemom prema kliničkoj izliječenosti u trenutku posjeta za kraj intravenoznog liječenja i kasnog posjeta za praćenje u ispitanika koji su imali barem 1 identificirani patogen i u ispitanika koji su mikrobiološki procjenjivi.
•Utvrditi učinkovitost ceftazidim-avibaktama u kombinaciji s metronidazolom u usporedbi s meropenemom prema kliničkoj izliječenosti u trenutku posjeta za kraj liječenja, posjeta za utvrđivanje izliječenosti i kasnog posjeta za praćenje u ispitanika koji su klinički procjenjivi.
itd. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. 18 to 90 years of age inclusive.
2. Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 1 week after.
3. Intraoperative/postoperative enrollment with confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis.
4. Confirmation of infection by surgical intervention within 24 hours of entry: evidence of systemic inflammatory response; physical findings consistent with intra-abdominal infection; supportive radiologic imaging findings of intra-abdom infections. |
Croatian: 1. Ispitanici moraju potpisati informirani pristanak prije provođenja bilo kojeg postupka vezanog uz ispitivanje. Međutim, ako ga ispitanik nije sposoban dati , to može učiniti njegov zakonski ovlašteni predstavnik u skladu sa smjernicama ustanove. Ispitanici koji u trenutku probira nisu bili pri svijesti ili je ispitivač smatrao da nisu klinički sposobni dati pristanak, ali su uključeni u ispitivanje pristankom zakonski ovlaštenog predstavnika, moraju dati vlastiti pisani informirani pristanak za nastavak sudjelovanja čim se dovoljno oporave, u skladu s lokalnim propisima.
2. Ispitanici moraju biti u dobi između 18 i 90 godina.
3. Ispitanice mogu sudjelovati u kliničkom ispitivanju ako ispunjavaju sljedeće kriterije:
(a) kirurški su sterilizirane, u postmenopauzi su barem godinu dana ili je njihovom seksualnom partneru napravljena vazektomija
ILI
(b) ako su sposobne zatrudnjeti i ako su ispunjeni svi sljedeći uvjeti:
• imale su normalne mjesečnice 3 mjeseca prije uključivanja u ispitivanje, i
• imale su negativan serumski test na trudnoću [ß humanog korionskog gonadotropina (ß-hCG)] 1 dan prije uključivanja u ispitivanje (ako se rezultati serumskog testa na trudnoću ne mogu pribaviti prije davanja ispitivanog lijeka, ispitanica se smije uključiti na temelju negativnog urinskog testa na trudnoću, ali se serumski (ß-hCG)] test na trudnoću ipak treba napraviti), i
• pristaju na to da tijekom liječenja i bar 7 dana nakon primanja zadnje doze intravenoznog ispitivanog lijeka koriste visoko učinkovite metode kontracepcije kao što su unutarmaternični usadak (s bakrenom ovojnicom), unutarmaternični sustav temeljen na levonogestrelu (na primjer, Mirena®) i injekcije medroksiprogesterona (Depo-Provera®) ili se suzdržavati od spolnih odnosa.
Oralna kontracepcijska sredstva ne mogu se koristiti kao jedina metoda kontracepcije jer još nije utvrđen utjecaj lijeka CAZ-AVI na njih. Barijerne metode (kao što su kondom za muškarce ili dijafragma sa spermicidom) mogu se koristiti uz još jednu prihvatljivu metodu kontracepcije (ne oralnu).
|
|
| E.4 | Principal exclusion criteria |
1. Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation.
2. Patient is diagnosed with traumatic bowel perforation undergoing surgery within 12 hours; perforation of gastroduodenal ulcers undergoing surgery within 24 hours. Other intra-abdominal processes in which primary etiology is not likely to be infectious.
3. Patient has suspected intra-abdominal infections due to fungus, parasites, virus or tuberculosis.
4. Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness.
5. Patient has evidence of sepsis with shock not responding to IV fluid challenge or anticipated to require the administration of vasopressors for > 12 hours. |
Croatian: 1. Ispitaniku je dijagnosticirana traumatska perforacija crijeva koja se mora operirati u roku od 12 sati; perforacija čireva na želucu i/ili dvanaesniku koja se mora operirati u roku od 24 sata; ostali intraabdominalni procesi čija primarna etiologija vjerojatno nije infektivna.
2. Ispitanik ima apsces trbušnog zida ili opstrukciju crijeva bez perforacije ili ishemičnu stjenku crijeva bez perforacije.
3. Ispitanik ima jednostavnu upalu žučnog mjehura, gangrenoznu upalu žučnog mjehura bez puknuća, nekompliciranu upalu crvuljka, akutnu gnojnu upalu žučovoda, inficiranu nekrotizirajuću upalu gušterače ili apsces gušterače.
4. Ispitanik čija će operacija uključivati abdominalnu plastiku u više faza, tehniku „otvorenog abdomena” ili marsupializaciju. Svrha ovoga kriterija je ta da isključi pacijente kojima se abdomen ostavlja otvoren, a posebice one koji imaju planiranu ponovnu operaciju.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| To assess the proportion of patients with clinical cure in the microbiological modified intent-to-treat analysis set. |
Primarna ishodna varijabla učinkovitosti
Croatian: Primarna ishodna varijabla učinkovitosti je omjer ispitanika s kliničkom izliječenošću u trenutku posjeta za utvrđivanje izliječenosti u statističkom skupu mikrobiološke modificirane namjere liječenja.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At the test of cure visit |
| Croatian: pri posjetu za utvrđivanje izlječenja |
|
| E.5.2 | Secondary end point(s) |
1. To assess the proportion of patients with clinical cure in the microbiologically evaluable analysis set.
2. To assess the proportion of patients with clinical cure in the microbiological modified intent-to-treat and microbiologically evaluable analysis sets.
3. To assess the proportion of patients with clinical cure in the clinically evaluable anlaysis set.
4. To assess the proportion of patients with a favorable per-patient microbiological response in the microbiological modified intent to treat and microbiologically evaluable analysis sets.
5. To assess the proportion of favorable per-pathogen microbiological response in the microbiological modified intent to treat and microbiologically evaluable anlaysis sets.
6. To assess the favorable per-pathogen microbiologic response by minimum inhibitory concentration (MIC) categories in the microbiological modified intent to treat and microbiologically evaluable analysis sets.
7. To assess the favorable per-patient clinical response and favorable per patient microbiological response for patients infected with ceftazidime-resistant pathogens in the microbiological modified intent to treat and microbiologically evaluable analysis sets.
8. To assess the proportion of patients with a favorable per pathogen microbiological response for patients infected with ceftazidime-resistant pathogens in the microbiological modified intent to treat and microbiologically evaluable anlaysis sets.
9. To assess the time to first defervescence in the clinically evaluable and microbiologically evaluable anlaysis sets for patients who have fever at study entry.
10. To assess the safety and tolerability by incidence and severity of adverse events and serious adverse events, vital signs, clinical laboratory tests, ECGs and physical exams. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. at the test of cure visit
2. at the end of treatment and late follow-up visits
3. at the end of treatment, test of cure and late follow-up visits
4. at the end of treatment, test of cure and late follow-up visits
5. at the end of treatment, test of cure and late follow-up visits
6. at the end of treatment, test of cure and late follow-up visits
7. at the test of cure visit
8. at the test of cure visit
9. while on IV study therapy
10. study duration |
Croatian: Sekundarne ishodne varijable učinkovitosti uključuju sljedeće:
− udio ispitanika s kliničkom izliječenošću u trenutku posjeta za utvrđivanje izliječenosti u statističkom skupu mikrobiološki procjenjivih i u proširenom statističkom skupu mikrobiološki procjenjivih;
− udio ispitanika s kliničkom izliječenošću u trenutku posjeta za kraj liječenja i kasnog posjeta za praćenje u statističkim skupovima mikrobiološke modificirane namjere liječenja i mikrobiološki procjenjivih te proširenom statističkom skupu mikrobiološki procjenjivih;
itd. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| biomarkers and microbiology cultures |
| Croatian: biomarkeri i mikrobiološke kulture |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 55 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Belgium |
| Brazil |
| Bulgaria |
| Canada |
| Czech Republic |
| Hungary |
| India |
| Israel |
| Italy |
| Mexico |
| Peru |
| Portugal |
| Romania |
| Russian Federation |
| South Africa |
| Spain |
| Taiwan |
| Thailand |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| last subject last visit |
| Croatian: Zadnji posjet zadnjeg ispitanika |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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