E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart Failure |
Hjertesvigt |
|
E.1.1.1 | Medical condition in easily understood language |
Decreased function of the heart (heart failure) |
Nedsat pumpefunktion af hjertet (hjertesvigt) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019279 |
E.1.2 | Term | Heart failure |
E.1.2 | System Organ Class | 100000004849 |
|
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 test if infusion of the V1A/V2-receptor blocker conivaptan improves hemodynamics and physical capacity in HF patients on optimal HF medical therapy and to improve understanding of the role of vasopressin in HF. |
At undersøge om infusion af V1A/V2-receptor blokkeren conivaptan medfører en forbedring af hæmodynamikken og arbejdskapaciteten hos hjertesvigtpatienter i optimal medicinsk behandling samt at forbedre forståelsen af vasopressinsystemet ved hjertesvigt. |
|
E.2.2 | Secondary objectives of the trial |
Not applicable |
Ikke anført |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Age > 18 years
-LVEF < 45 %
-Treatment with beta-blockers and ACE-inhibitors for at least 1 month
-NYHA-class II-III
-Given informed consent
Women, who have not yet entered menopause (defined as no menstrual bleeding in the last 12 months), will provide a negative urine HCG before entering the study |
-Alder > 18 år
-Kendt LVEF < 45 %
-Kendt hjertesvigtbehandling med beta-blokker og ACE-hæmmer i minimum 1 måned
-NYHA-klasse II-III
-Underskrevet informeret samtykke
Kvinder der endnu ikke er indtrådt i menopause (defineret som udeblivende menstruation i minimum 1 år) skal aflevere negativ urin HCG inden indtrædelse i studiet.
|
|
E.4 | Principal exclusion criteria |
-Signs of symptomatic or ongoing myocardial ischemia
-Presence of hypovolemic hyponatremia (as judged by the investigator)
-Clinical signs of volume depletion or dehydration
-Hypernatremia (P-Na+) > 145 mmol/L
-Chronic obstructive pulmonary disease (FEV1 < 1L)
-Supine systolic blood pressure < 85 mmHg
-Significant orthostatic hypotension
-standing blood pressure < 80 mmHg or a blood pressure drop > 20 mmHg when changing from a supine to a standing position
-Uncontrolled hypertension
-Uncontrolled cardiac arrhythmias
-Untreated serious hypothyroidism
-Adrenal insufficiency
-Poor echocardiographic window
-Not able to perform exercise testing
-Permanent atrial fibrillation or atrial fluttering
-Planned coronary by-pass surgery
-Moderate hepatic impairment (ALAT/ASAT > 3 UNL)
-Presence of other diseases affecting treatment with conivaptan or the evaluation of safety
-Severely decreased kidney function (eGFR < 20 ml/min)
-Serum K+< 3.5 or > 5.5 mmol/L
-Conivaptan intolerability
-Corn allergy
-Treatment with potent CYP3A-inhibitors (ketoconazole, otrakonazole, clarithromycin, ritonavir, indinavir)
-Treatment with arginine vasopressin, oxytocin, desmopressin and other medications for the treatment of hyponatremia (lithium salts, urea and demeocycline)
-Warfarin treatment
-Presence of infection or active bleeding
-Need of inotropic circulatory support within the last 30 days
-Pregnant women or fertile women not taking safe contraception
-Women who are breastfeeding
-Hemodynamically significant heart valve disease estimated by echocardiography
-The ability to understand written and oral Danish
-Contraindication to insertion of Swan-Ganz catheter
|
-Tegn til pågående symptomatisk eller asymptomatisk myokardie iskæmi
-Tilstedeværelse af hypovolæmisk hyponatriæmi vurderet ved investigator (kliniske tegn til volumendepletion eller dehydrering)
-Hypernatriæmi (P-Na+) > 145 mmol/L
-Kronisk obstruktiv lungesygdom (FEV1 < 1 L)
-Liggende systolisk blodtryk < 85 mmHg
-Betydende ortostatisk hypotension
-Stående systolisk blodtryk < 80 mmHg eller et blodtryksfald > 20 mmHg ved overgang fra liggende til stående stilling
-Ukontrolleret hypertension
-Ukontrollerede arytmier
-Ubehandlet alvorlig hypothyroidisme
-Binyrebark insufficiens
-Ringe ekkokardiografisk indblik
-Kan ikke gennemføre arbejdstest
-Permanent atrieflimren/flagren
-Planlagt koronar bypass operation
-Betydende leverpåvirkning (ALAT/ASAT > x 3 ULN)
-Tilstedeværelse af anden sygdom, der kan påvirke behandling med conivaptan eller evaluering af safety
-Svært nedsat nyrefunktion (eGFR < 20 mL/min)
-Serum kalium < 3.5 eller > 5.5 mM/L
-Kendt overfølsomhed for conivaptan
-Kendt allergi overfor majs (korn) produkter
-Behandling med potente CYP3A inhibitorer (ketokonazol, itrakonazol, clarithromycin, ritonavir og indinavir)
-Behandling med arginin vasopressin, oxytocin, desmopressin og andre medikamenter til behandling af hyponatriæmi (lithiumsalte, urea og demeocyclin)
-Behandling med marevan
-Aktiv infektion eller blødning
-Behov for inotropisk kredsløbsstøtte inden for de sidste 30 dage
-Gravide eller kvinder i den fertile alder der ikke tager sikker kontraception.
-Ammende kvinder
-Hæmodynamisk betydende hjerteklapsygdom vurderet ved ekkokardiografi
-Skal kunne tale og forstå skriftligt og mundtligt dansk
-Kontraindikationer mod anlæggelse af Swan-Ganz kateter
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
-PCWP at the submaximal exercise intensity of 50 % of the maximal exercise capacity |
-PCWP ved submaksimalt arbejde ved 50 % af den maksimale arbejdsintensitet |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
-Cardiac index (CI) during submaximal exercise before and during conivaptan-infusion
-Pulmonary and peripheral vascular resistance during exercise
-Left ventricular end diastolic diameter during exercise
-The Doppler-index of the left ventricular filling (E/e’) during exercise
-The change in BNP, MR-ANP and copeptin from rest to submaximal exercise
|
-Cardiac index (CI) under submaksimalt arbejde før og under infusion af conivaptan
-Pulmonal og vaskulær modstand under arbejde
-Venstre ventrikel slutdiastolisk diameter under arbejde
-Dopplerindex af venstre ventrikels fyldning (E/e´) under arbejde
-Ændring BNP, MR-ANP og copeptin fra hvile til submaksimalt arbejde |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 visit of the last subject |
Sidste forsøgspersons sidste besøg |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |