protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT03329092 | 8.4.1 | Protocol-Specified Serious Adverse Events | There are no protocol-specified SAEs in this study. All SAEs will be reported to Pfizer Safety by the investigator as described in previous sections, and will be handled as SAEs in the safety database. | [] |
NCT03329092 | 8.4.2 | Adverse Events Based on Signs and Symptoms | All AEs spontaneously reported by the subject or care provider or reported in response to the open question from the study personnel: 'Have you had any health problems since the previous visit/you were last asked?', or revealed by observation will be collected and recorded in the CRF. When collecting AEs, the recording... | [] |
NCT03329092 | 8.4.3 | Adverse Events Based on Examinations and Tests | The results from protocol mandated laboratory tests and vital signs will be summarized in the CSR. Deterioration as compared to Baseline in protocol-mandated laboratory values, vital signs and ECG should therefore only be reported as AEs if they fulfil any of the AE criteria or are the reason for discontinuation of tre... | [] |
NCT03329092 | 8.4.4 | Exceptions from Standard Adverse Events Collection | Where there is deterioration in the condition for which the IV study treatment is being used, there may be uncertainty as to whether this is lack of efficacy, disease progression or constitutes an AE. In such cases, unless the Pfizer or reporting physician considers that the study treatment contributed to the deteriora... | [] |
NCT03329092 | 8.4.4.1 | Lack of Effect | Insufficient therapeutic effect will be captured as an efficacy outcome. Instances of, or discontinuation due to insufficient therapeutic effect (ie, lack of efficacy) should not be collected as AEs. A clinical failure should not be recorded as an AE. | [] |
NCT03329092 | 8.4.4.2 | Disease Progression | Disease progression can be considered as a worsening of a subject's condition attributable to the disease for which the IP is being studied. It may be an increase in the severity of the disease under study and/or increases in the symptoms of the disease. Expected progression of the disease under study and /or expected ... | [] |
NCT03329092 | 8.4.5 | Potential Cases of Drug-Induced Liver Injury | Humans exposed to a drug who show no sign of liver injury (as determined by elevations in transaminases) are termed "tolerators," while those who show transient liver injury, but adapt are termed "adaptors." In some subjects, transaminase elevations are a harbinger of a more serious potential outcome. These subjects fa... | [] |
NCT03329092 | 8.4.6 | Exposure to the Investigational Product During Pregnancy or Breastfeeding, and Occupational Exposure | Exposure to the investigational product under study during pregnancy or breastfeeding and occupational exposure are reportable to Pfizer Safety within 24 hours of investigator awareness. | [] |
NCT03329092 | 8.4.6.1 | Exposure During Pregnancy | For both unapproved/unlicensed products and for marketed products, an exposure during pregnancy (EDP) occurs if:
• A female becomes, or is found to be, pregnant either while receiving or having been exposed (eg, because of treatment or environmental exposure) to the investigational product; or the female becomes or is... | [] |
NCT03329092 | 8.4.6.2 | Exposure During Breastfeeding | Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of an associated SAE, to Pfizer Safety within 24 hours of the investigator's awareness, using the CT SAE Report Form. An exposure during breastfeeding report is not created when a Pfizer drug specifically approved for use in breas... | [] |
NCT03329092 | 8.4.6.3 | Occupational Exposure | An occupational exposure occurs when, during the performance of job duties, a person (whether a healthcare professional or otherwise) gets in unplanned direct contact with the product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the inv... | [] |
NCT03329092 | 8.4.7 | Medication Errors | Other exposures to the investigational product under study may occur in clinical trial settings, such as medication errors.
| Safety Event | RecordedontheCRF | Reported on the CT SAEReport Form to PfizerSafetyWithin 24 HoursofAwareness |
|----------------------|----------------... | [] |
NCT03329092 | 8.4.7.1 | Overdose | Overdose is defined as a dose of study drug administered to a subject in excess of that specified in Section 5.6. Overdose does not automatically make an AE/SAE but if the consequences of the overdose are accompanied by an AE or serious for example death or hospitalization, the event is AE or SAE and should be reported... | [] |
NCT03329092 | 8.5 | Management of Laboratory Safety | If necessary, ATM may be cleared from the serum by hemodialysis and/or peritoneal dialysis. ATM has been shown to be cleared from the serum by continuous arteriovenous hemofiltration. AVI may also be cleared from the serum by hemodialysis (55% of the AVI dose was removed in 4 hours in a group of subjects with ESRD). | [] |
NCT03329092 | 8.5.1 | Renal Function | CrCL will be monitored at Screening, Baseline, Day 2 through Day 4 (daily) (and Day 5 if PK sample collected on Day 5) and as clinically indicated and dose of study drug will be adjusted accordingly throughout the study. Determination of creatinine will be part of each safety laboratory until TOC inclusive, ie, every 3... | [] |
NCT03329092 | 8.5.2 | Monitoring of Liver-related Laboratory Parameters | If a subject reaches an ALT or AST >3 x ULN and has not met the discontinuation criteria, the following enhanced monitoring and subject follow-up will be instigated:
- Collection of clinical and historical information to determine the cause of ALT and/or AST elevations (and completing the relevant CRFs modules);
- Fre... | [] |
NCT03329092 | 9 | DATA ANALYSIS/STATISTICAL METHODS | Detailed methodology for summary and statistical analyses of the data collected in this study is outlined here and further detailed in a statistical analysis plan (SAP), which will be maintained by the sponsor. The SAP may modify what is outlined in the protocol where appropriate; however, any major modifications of th... | [] |
NCT03329092 | 9.1 | Sample Size Determination | The study will randomize up to approximately 425 subjects in a 2:1 randomization ratio (approximately 283 subjects to ATM-AVI ±MTZ and approximately 142 subjects to MER ±COL) with serious infections proven or strongly suspected to be caused by MDR pathogens, including those producing MBLs. Current literature indicates ... | [] |
NCT03329092 | 9.2 | Definitions of Analysis Sets | [] | |
NCT03329092 | 9.2.1 | Efficacy Analysis Set | [] | |
NCT03329092 | 9.2.1.1 | Intent-To-Treat (ITT) Analysis Set | The ITT analysis set will include all randomized subjects regardless of receipt of study drug. Subjects in the ITT analysis set will be analyzed according to the treatment they are randomized to. The ITT analysis set will be used to evaluate the primary, secondary and tertiary objectives. | [] |
NCT03329092 | 9.2.1.2 | Clinically Evaluable (CE) Analysis Set | The CE analysis set is defined as all subjects who:
- Meet the definition of the ITT analyses.
- Meet disease criteria for diagnosis of cIAI, or HAP/VAP.
- Received at least 48 hours of study treatment (ATM-AVI ±MTZ or MER ±COL) or received <48 hours of study treatment before discontinuing study drug due to an AE.
- ... | [] |
NCT03329092 | 9.2.1.3 | Microbiological Intent-To-Treat (micro-ITT) Analysis Set | The microbiological Intent-To-Treat (micro-ITT) analysis set is a subset of the ITT analysis set and includes all subjects who have at least 1 Gram-negative pathogen in an adequate initial/prestudy culture. Subjects with inherently resistant pathogens (monomicrobial infections due to any *Acinetobacter* spp.), and thos... | [] |
NCT03329092 | 9.2.1.4 | Microbiologically Evaluable (ME) Analysis Set | The ME analysis set includes all subjects included in both micro-ITT and CE analysis sets, and had at least 1 Gram-negative pathogen. The ME analysis set will be used to evaluate selected secondary and tertiary objectives. | [] |
NCT03329092 | 9.2.1.5 | Modified Intent-To-Treat Analysis Set | The modified ITT (MITT) analysis set will include all randomized subjects who receive any amount of study drug. Subjects in the MITT analysis set will be analyzed according to the treatment they received. The MITT analysis set will be used in the sensitivity analysis of the primary endpoint. | [] |
NCT03329092 | 9.2.1.6 | Microbiological Modified Intent-To-Treat (micro-MITT) Analysis Set | The microbiological modified ITT (micro-MITT) analysis set is a subset of the micro-ITT analysis set and includes all subjects who receive any amount of study drug. The
micro-MITT analysis set will be used in sensitivity analysis of microbiological response endpoints. | [] |
NCT03329092 | 9.2.2 | Safety Analysis Set | The safety analysis set will be used for reporting safety data and will include all subjects who received any amount of IV study treatment. Subjects in the safety analysis sets will be analyzed according to the treatment they receive. | [] |
NCT03329092 | 9.2.3 | Population Pharmacokinetic (popPK) Analysis Set | The population pharmacokinetic (popPK) analysis set will include all subjects who have at least 1 plasma concentration data assessment available for ATM-AVI±MTZ and will be used to report all PK data. | [] |
NCT03329092 | 9.2.4 | Other Analysis Sets | [] | |
NCT03329092 | 9.2.4.1 | All Subjects Analysis Set | This analysis set will compromise all subjects enrolled into the study and will be used for reporting of disposition. | [] |
NCT03329092 | 9.3 | Outcome Measures for Analyses | [] | |
NCT03329092 | 9.3.1 | Primary Outcome Variable | The primary efficacy outcome measure is the proportion of subjects with clinical cure at TOC in the ITT and CE analysis sets. For the US regulatory submission, the ITT analysis set will be used for the primary analysis while CE analysis set will be the secondary analysis. The proportion of subjects with clinical cure f... | [] |
NCT03329092 | 9.3.2 | Secondary Outcome Variables | The secondary outcome measures are:
- Proportion of subjects with clinical cure at TOC visit in the micro-ITT and ME analysis sets.
- Proportion of subjects with clinical cure at the TOC visits by infection type in the ITT and CE analysis sets.
- Proportion of subjects with clinical cure at the TOC visit for subjects ... | [] |
NCT03329092 | 9.3.3 | Tertiary Outcome Variables | - Proportion of subjects with clinical cure at the EOT visit in the ITT, micro-ITT, CE and ME analysis sets.
- Proportion of subjects with clinical cure at the EOT visit by infection type in the ITT and CE analysis sets.
- Proportion of subjects with clinical cure at the EOT visit for subjects with MBL-positive pathoge... | [] |
NCT03329092 | 9.3.4 | Exploratory Outcome Variables | The exploratory outcome measures assessing the outcomes are:
- Summary of total score for the composite endpoint of symptom-based objective clinical measures (ITT and CE analysis sets).
- Proportion of subjects who died on or before 14 days after randomization.
- For the health utilization objective:
- Length of hos... | [] |
NCT03329092 | 9.3.5 | Safety Variables | The following safety data will be collected: AEs, physical examination, vital signs, ECGs and laboratory values. | [] |
NCT03329092 | 9.4 | Methods for Statistical Analyses | All data will be presented by treatment arm. Descriptive statistics (number, mean, standard deviation [SD], median, minimum, and maximum) will be provided for continuous variables, and counts and percentages will be presented for categorical variables.
No formal hypothesis testing will be performed for this study. Any... | [] |
NCT03329092 | 9.4.1 | Analysis of the Primary Variable | The primary descriptive efficacy analysis (for non-US countries) will be the estimate of the clinical cure rate and 95% confidence interval (CI) in each treatment arm (ATM-AVI ±MTZ and MER ±COL) in the ITT and CE co-primary analysis sets. The estimate of the clinical cure rate and 95% CI in each treatment arm in the IT... | [] |
NCT03329092 | 9.4.2 | Analysis of the Secondary/Tertiary Variable(s) | Secondary and tertiary efficacy outcome measures will be assessed and presented using the same methods as described in Section 9.4.1. For descriptive secondary/tertiary outcome measures, number and percentage in each treatment arm will be tabulated. Summaries will be presented for the overall population, and also split... | [] |
NCT03329092 | 9.4.3 | Subgroup Analysis | Subgroup analysis may include subject characteristics, disease severity, prior antibiotic use, infection type and pathogen resistance type. More details on the subgroup analyses will be provided in the SAP. | [] |
NCT03329092 | 9.4.4 | Interim Analysis | No formal interim analysis will be conducted for this study. However, as this is an open-label study, the sponsor may conduct reviews of the data which will include no summaries of data by treatment arm during the course of the study for the purpose of safety assessment, and/or to support clinical development. | [] |
NCT03329092 | 9.4.5 | Supportive Analyses | Additional descriptive analyses of the primary endpoint (clinical cure rate) will be performed for the effect of protocol-allowed additional antibiotics (eg, Gram-positive antibiotics, aminoglycosides).
An additional descriptive analysis will be performed for clinical cure at TOC using the MITT population which compri... | [] |
NCT03329092 | 9.4.6 | Exploratory Analysis | Subjects will be summarized by the value of their composite score of symptom-based objective clinical measures.
The proportion of subjects who died on or before 14 days after randomization will be presented by treatment arm.
Further details on the analysis methods for response endpoint utilizing objective measures of... | [] |
NCT03329092 | 9.4.7 | Analysis Methods for Safety Variables | AEs will be summarized by means of counts summaries by preferred term separately for the study periods (treatment period [from first dose to EOT], from EOT to LFU, and for the full study period [from first dose to LFU].) All AEs and treatment emergent adverse events (TEAEs) will be listed (including prior to first dose... | [] |
NCT03329092 | 9.5 | Data Monitoring Committee | This study will use an external data monitoring committee (E-DMC).
The E-DMC will be responsible for ongoing monitoring of the safety of subjects in the study according to the E-DMC Charter. The recommendations made by the E-DMC to alter the conduct of the study will be forwarded to Pfizer for final decision. Pfizer w... | [] |
NCT03329092 | 9.6 | Independent Clinical Hepatologist Review of Potential Hy's Law Cases | With regards to any cases of potential Hy's Law (PHL), the Pfizer Medical Monitor will initially review the case (as described in Appendix 4) and then the case will be referred for independent clinical hepatologist review. The independent clinical hepatology review will be unblinded to study treatment allocation. The i... | [] |
NCT03329092 | 9.7 | Independent Adjudication Committee | An independent adjudication committee consisting of at least three experts will be convened at regular intervals during the study. This independent adjudication committee is the central blinded assessor (see Section 5.2).
A charter will be in place for the adjudication committee. The adjudication committee will be bli... | [] |
NCT03329092 | 10 | QUALITY CONTROL AND QUALITY ASSURANCE | Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that the protocol and Good Clinical Practices (GCPs) are being followed. The monitors may review source documents to confirm that the data recorded on CRFs are accurate. The investigator and institution will allow Pfizer monitors... | [] |
NCT03329092 | 11 | DATA HANDLING AND RECORD KEEPING | [] | |
NCT03329092 | 11.1 | Case Report Forms/Electronic Data Record | As used in this protocol, the term CRF should be understood to refer to either a paper form or an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject. The completed original CRFs are the sole property of Pfizer ... | [] |
NCT03329092 | 11.2 | Record Retention | To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the investigator agrees to keep records, including the identity of all participating subjects (sufficient information to link records, eg, CRFs and hospital records), all original signed informed consent documents, copies of all CRFs... | [] |
NCT03329092 | 11.3 | Data Protection | All parties will comply with all applicable laws, including laws regarding the implementation of organizational and technical measures to ensure protection of participant data.
Participants' personal data will be stored at the study site in either an encrypted electronic and/or paper form and will be password protecte... | [] |
NCT03329092 | 12 | ETHICS | [] | |
NCT03329092 | 12.1 | Regulatory and Ethical Considerations | This study will be conducted in accordance with the protocol and with the following:
- Consensus ethical principles derived from international guidelines, including the Declaration of Helsinki and CIOMS International Ethical Guidelines;
- Applicable ICH GCP guidelines;
- Applicable laws and regulations, including appl... | [] |
NCT03329092 | 12.1.1 | Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP | In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable regulatory authority in any area of the world, or if the investigator is aware of any new information that might influence the evaluation of the benefits and risks of the study intervention, Pfizer should be informed immediately... | [] |
NCT03329092 | 12.2 | Subject Information and Consent | All parties will ensure protection of subject personal data and will not include subject names or other identifiable data in any reports, publications, or other disclosures, except where required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, subject names, addresses, and oth... | [] |
NCT03329092 | 12.3 | Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP | In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable regulatory authority in any area of the world, or if the investigator is aware of any new information that might influence the evaluation of the benefits and risks of the investigational product, Pfizer should be informed immedi... | [] |
NCT03329092 | 13 | DEFINITION OF END OF TRIAL | [] | |
NCT03329092 | 13.1 | End of Trial in a Member State | End of trial in a Member State of the European Union is defined as the time at which it is deemed that a sufficient number of subjects have been recruited and completed the study as stated in the regulatory application (ie, clinical trial application [CTA]) and ethics application in the Member State. Poor recruitment (... | [] |
NCT03329092 | 13.2 | End of Trial in All Other Participating Countries | End of trial in all other participating countries is defined as last subject last visit (LSLV). | [] |
NCT03329092 | 14 | SPONSOR DISCONTINUATION CRITERIA | Premature termination of this study may occur because of a regulatory authority decision, change in opinion of the IRB/EC, or investigational product safety problems, or at the discretion of Pfizer. In addition, Pfizer retains the right to discontinue development of ATM-AVI at any time.
If a study is prematurely termi... | [] |
NCT03329092 | 15 | PUBLICATION OF STUDY RESULTS | [] | |
NCT03329092 | 15.1 | Communication of Results by Pfizer | Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the results of studies on [www.clinicaltrials.gov](http://www.clinicaltrials.gov/) (ClinicalTrials.gov), the European Clinical Trials Database (EudraCT), and/or [www.pfizer.com,](http://www.pfizer.com/) and other public registrie... | [
"[www.clinicaltrials.gov](http://www.clinicaltrials.gov/)",
"EudraCT",
"[www.pfizer.com](http://www.pfizer.com/)"
] |
NCT03329092 | 15.2 | Publications by Investigators | Pfizer supports the exercise of academic freedom and has no objection to publication by the principal investigator (PI) of the results of the study based on information collected or generated by the PI, whether or not the results are favorable to the Pfizer product. However, to ensure against inadvertent disclosure of ... | [] |
NCT03329092 | 16 | REFERENCES | - 1. Azim A, Dwivedi M, Rao PB, Baronia AK, Singh RK, Prasad KN, et al. Epidemiology of bacterial colonization at intensive care unit admission with emphasis on extendedspectrum beta-lactamase- and metallo-beta-lactamase-producing Gram-negative bacteria—an Indian experience. J Med Microbiol 2010;59:955-60.
- 2. Metroni... | [
"Appendix 1. Abbreviations",
"Appendix 2. International Airline Transportation Association (IATA) 6.2 Guidance Document",
"Labelling and shipment of biohazard samples",
"Appendix 3. Calculation of Estimated Creatinine Clearance",
"Calculation of the estimated creatinine clearance",
"Appendix 4. Actions Re... |
NCT03355664 | 1 | LIST OF ABBREVIATIONS | ACPR Adequate clinical and parasitological response
ACT Artemisinin-based combination therapy
AE Adverse event
A/L Artemether-lumefantrine
AQ Amodiaquine
AUC Area under the (plasma concentration-time) curve
CRF Case record form
CTSG Clinical Trials Support Group (MORU)
CYP3A4 Cytochrome P450 3A4 DHA Dihydroarte... | [] |
NCT03355664 | 2 | SYNOPSIS | | StudyTitle | Amulti-centre,open-labelrandomisedtrialtoassesstheefficacy,safetyandtolerabilityoftheTripleACTartemether-lumefantrine+amodiaquine(AL+AQ)comparedtotheACTartemether-lumefantrine(AL)inuncomplicatedfalciparummalariainCambodiaandVietnam ... | [
"Drugs",
"Primaquine"
] |
NCT03355664 | 3 | BACKGROUND AND RATIONALE | Artemisinin combination therapies (ACTs) have been a major driving force behind substantial reductions in global malaria morbidity and mortality over recent years. However, further gains are threatened by the recent emergence of artemisinin resistance in Southeast Asia, a region which has been the epicentre for the evo... | [] |
NCT03355664 | 3.1 | Background | The Tracking Resistance to Artemisinin Collaboration (TRAC) study was focused on mapping the spread of artemisinin resistance by conducting a multi-centre clinical trial, coordinated by the Mahidol Oxford Research Unit (MORU) at sites in Asia (N=13) and Africa (N=3). This study measured individual parasite clearance ra... | [] |
NCT03355664 | 3.2 | Study Rationale | The principle that multiple drugs with independent mechanisms of action prevent the emergence of drug resistance is proven in a range of human diseases. In HIV and tuberculosis for example, the occurrence and spread of drug resistance can be prevented by use of a combination of three or more antiretroviral or antimycob... | [] |
NCT03355664 | 3.3 | Proposed activities |
The study of artemether-lumefantrine or artemether-lumefantrine combined with amodiaquine will be a two-arm randomised open label comparative study. Based on the relatively safe and limited side effect profiles of both drugs, no life-threatening interactions between lumefantrine and amodiaquine are expected. In fact,... | [
"Artemether-lumefantrine+amodiaquine TACT study",
"Activities/outcomes"
] |
NCT03355664 | 4 | OBJECTIVES | [] | |
NCT03355664 | 4.1 | Primary Objective | To compare the efficacy of the TACT artemether-lumefantrine+amodiaquine versus the ACT artemether-lumefantrine as defined by the 42-day PCR corrected adequate clinical and parasitological response (ACPR). | [] |
NCT03355664 | 4.2 | Secondary Objectives | - To compare the efficacy of the TACT artemether-lumefantrine+amodiaquine versus ACT artemether-lumefantrine as defined by the 42-day PCR ACPR according to site/geographical region.
- To assess and compare *P*. *falciparum* parasite clearance rates of the standard ACT and study TACT
- To assess and compare fever cleara... | [] |
NCT03355664 | 5 | TRIAL DESIGN | [] | |
NCT03355664 | 5.1 | Study sites | The study will take place at 2 sites in Cambodian and 2 sites in Vietnam (Appendix 3). | [] |
NCT03355664 | 5.2 | Summary of trial design | An open-label randomised trial comparing the Triple ACT (TACT) artemether-lumefantrine+amodiaquine with artemether-lumefantrine ACT treatment, evaluating efficacy, safety, tolerability and artemisinin and partner drug resistance in four sites. | [] |
NCT03355664 | 5.3 | Study duration | The recruitment phase of the study is expected to last 24 months once a site starts to recruit. The first sites intend to start recruiting patients in October 2017. Training will precede study execution by up to 1 month. Data management and analysis, sample analysis (PK, *in vitro*, molecular markers) and report writin... | [] |
NCT03355664 | 5.4 | Primary and secondary endpoints | [] | |
NCT03355664 | 5.4.1 | Primary Endpoint | 42-day PCR corrected efficacy defined as adequate clinical and parasitological response (ACPR). WHO definition: absence of parasitaemia at day 42 irrespective of axillary temperature and without previously meeting any of the WHO criteria for early or late treatment failure, or late parasitological failure. | [] |
NCT03355664 | 5.4.2 | Secondary Endpoints | - 42-day PCR corrected efficacy defined as adequate clinical and parasitological response (ACPR) according to site/geographic region.
- Parasite clearance half-life assessed by microscopy as primary parameter to determine parasite clearance
- Additional parameters of parasite clearance dynamics
- Fever clearance time (... | [] |
NCT03355664 | 5.5 | Trial Participants | [] | |
NCT03355664 | 5.5.1 | Overall Description of Trial Participants | Male and non-pregnant female patients aged between 2 years and 65 years with acute uncomplicated falciparum malaria are the target study population. All study patients must meet the applicable inclusion and exclusion criteria. | [] |
NCT03355664 | 5.5.2 | Inclusion criteria | • Male or female, aged from 2 years to 65 years old.
- Acute uncomplicated *P. falciparum* malaria, confirmed by positive blood smear with asexual forms of *P. falciparum* (or mixed with non-falciparum species)
- Asexual *P. falciparum* parasitaemia: 16 to 200,000/uL, determined on a thin or thick blood film
- Fever d... | [] |
NCT03355664 | 5.5.3 | Exclusion criteria | - Signs of severe/complicated malaria
- Haematocrit 450 milliseconds at moment of presentation
- Documented or claimed history of cardiac conduction problems
- Previous participation in the current study or another study in the previous 3 months
- Glasgow coma scale 4.0 mmol/L (if measured through point of care test)... | [
"Criteria for severe malaria (Adjusted from criteria used in SEAQUAMAT trial)"
] |
NCT03355664 | 6 | PROCEDURES | Study procedures will be performed according to the schedule of assessments (Appendix 1). This will require that participants are admitted to the hospital for at least 72 hours and continue to be followed up on a weekly basis for 6 weeks. This differs from what would be standard management of uncomplicated malaria in C... | [] |
NCT03355664 | 6.1 | Informed Consent | The patient (or witness if illiterate) or the parent/guardian of a minor must personally sign and date the latest approved version of the informed consent form before any study specific procedures are performed. Written and verbal versions of the participant information and informed consent in the local language will b... | [] |
NCT03355664 | 6.2 | Screening, Eligibility and Baseline Assessments | Patients who present at the participating sites will be screened to assess eligibility. Full consent (and assent if required) will be obtained before any enrolment procedures are conducted. It will be made clear from the outset that refusal to participate will not jeopardise subsequent antimalarial treatment. A screeni... | [] |
NCT03355664 | 6.2.1 | Demographics and Medical History | Basic demographic and epidemiological data (e.g. sex, age, address, bed net use, malaria risk factors, prior treatment and previous participation in this or previous studies), and a full medical history will be recorded by the study staff. | [] |
NCT03355664 | 6.2.2 | Physical Examination and Vital Signs | Physical examination will be conducted by a qualified study team member. Weight, height, pulse, blood pressure, respiratory rate, temperature, spleen and liver size will be recorded if palpable. | [] |
NCT03355664 | 6.2.3 | Drug history | All prescribed or over-the-counter and traditional medications used within the last 7 days will be recorded. Any drug allergies will be recorded. | [] |
NCT03355664 | 6.2.4 | Screening tests | These will be EDTA-anticoagulated blood for:
- A parasite count from Giemsa or Field stained thick and thin blood films
- Haematocrit
Urine pregnancy test for females of child bearing potential
Electrocardiograph to assess the QTc-interval | [] |
NCT03355664 | 6.3 | Randomisation and blinding | Patients who fulfil all the inclusion criteria and have none of the exclusion criteria will be randomised 1:1 to one of the two treatment arms according to a randomisation schedule. Randomisation will be in blocks of 8-12. Allocation will be done by drawing the next sequential numbered opaque envelope, which contains t... | [] |
NCT03355664 | 6.4 | Blood sampling | [] | |
NCT03355664 | 6.4.1 | On admission | Patients will have an intravenous catheter inserted for the first 24 hours. An SOP will be provided instructing how this is to be kept patent and how to take blood for protocol tests.
On study admission, immediately before drug administration, blood will be collected for the following:
- Repeat parasite count (thick ... | [] |
NCT03355664 | 6.4.2 | During hospitalisation | During hospitalisation, patients will have blood taken for malaria films at 4h, 6h, 8h and 12h and thereafter every 6 hours until parasite clearance (when two consecutive malaria slides are negative). In every case, malaria films will be performed at H4, H6, H8, H12, H24, H48 and H72 (even if two consecutive negative b... | [] |
NCT03355664 | 6.4.3 | Pharmacokinetic Study Sampling | PK sampling using EDTA-anticoagulated blood (1 ml per sampling occasion). Venous plasma will be used to evaluate the drug exposure to artemether, lumefantrine, and amodiaquine (and metabolites) using a conventional non-compartment analysis (first dose pharmacokinetics). All collected samples will also be analysed using... | [] |
NCT03355664 | 6.4.4 | Plasma HRP2 measurements | Plasma HRP2-levels will be measured on enrollment and subsequent timepoints and used for modelling of parasite dynamics on the residues of samples obtained for PK analysis (some sites). Therefore, no additional blood sampling will be needed for these measurements and analysis. | [] |
NCT03355664 | 6.4.5 | Host genotyping | Blood samples (dried blood blots) for human genotyping will be obtained and stored from all subjects recruited with subject's consent. Genotyping will be performed on the samples of subjects with suspected abnormal pharmacokinetics or pharmacodynamics (for instance in case of unexpected adverse events such as severe pr... | [] |
NCT03355664 | 6.4.6 | Blood volumes | The blood volumes for the protocol mandated tests are detailed in the study schedule (Appendix 1) and will vary slightly between sites depending on whether sites can perform all of the tests of this protocol e.g. not all sites will be able to do the full blood count, store the plasma PK samples or do the *ex vivo* para... | [] |
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