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Id Subject Object Predicate Lexical cue
T1 0-113 Sentence denotes An anti-CD6 antibody for the treatment of COVID-19 patients with cytokine-release syndrome: report of three cases
T2 115-123 Sentence denotes Abstract
T3 124-230 Sentence denotes In COVID-19, the inflammatory cytokine-release syndrome is associated with the progression of the disease.
T4 231-324 Sentence denotes Itolizumab is a monoclonal antibody that recognizes human CD6 expressed in activated T cells.
T5 325-424 Sentence denotes The antibody has shown to be safe and efficacious in the treatment of moderate to severe psoriasis.
T6 425-540 Sentence denotes Its effect is associated with the reduction of pro-inflammatory cytokines release, including IFN-γ, IL-6 and TNF-α.
T7 541-685 Sentence denotes Here, we report the outcome of three severe and critically ill COVID-19 patients treated with itolizumab as part of an expanded access protocol.
T8 686-756 Sentence denotes Itolizumab was able to reduce IL-6 concentrations in all the patients.
T9 757-856 Sentence denotes Two of the three patients showed respiratory and radiological improvement and were fully recovered.
T10 857-1011 Sentence denotes We hypothesize this anti-inflammatory therapy in addition to antiviral and anticoagulant therapy could reduce COVID-19 associated morbidity and mortality.
T11 1013-1025 Sentence denotes Lay abstract
T12 1026-1111 Sentence denotes In COVID-19 patients, inflammation is associated with the progression of the disease.
T13 1112-1192 Sentence denotes This inflammation comes from immune system activation in response to SARS-COV-2.
T14 1193-1271 Sentence denotes Itolizumab is an antibody that recognizes a protein expressed in immune cells.
T15 1272-1371 Sentence denotes The antibody has shown to be safe and efficacious in the treatment of moderate to severe psoriasis.
T16 1372-1461 Sentence denotes Its effect is associated with the reduction of inflammation and immune system activation.
T17 1462-1615 Sentence denotes Here, we report the outcome of three severe and critically ill COVID-19 patients treated with itolizumab as part of an expanded access clinical protocol.
T18 1616-1675 Sentence denotes Itolizumab was able to reduce inflammation in all patients.
T19 1676-1775 Sentence denotes Two of the three patients showed respiratory and radiological improvement and were fully recovered.
T20 1776-1930 Sentence denotes We hypothesize this anti-inflammatory therapy in addition to antiviral and anticoagulant therapy could reduce COVID-19 associated morbidity and mortality.
T21 1932-2040 Sentence denotes A group of COVID-19 patients develops severe or critical disease accompanied by the cytokine storm syndrome.
T22 2041-2219 Sentence denotes Cytokines are essential to the pathophysiology of disease and IL-6, IL-1 and TNF-α appear to be harmful, particularly in the context of the cytokine-release syndrome (CRS) [1,2].
T23 2220-2300 Sentence denotes CD6 is a membrane glycoprotein expressed primarily in mature, activated T cells.
T24 2301-2421 Sentence denotes Ligand binding of CD6, increases events such as adhesion, activation, proliferation, differentiation and survival [3–6].
T25 2422-2560 Sentence denotes In addition, CD6 mediates interaction between T cells and antigen-presenting cells, contributing to the maturation of immune synapses [6].
T26 2561-2768 Sentence denotes CD6-mediated costimulation contributes to the maturation of a Th1 pattern in human T cells and preferentially promotes a pro-inflammatory response characterized by the secretion of TNF-α, IL-6 and IFN γ [7].
T27 2769-2890 Sentence denotes The activated leukocyte-cell adhesion molecule (ALCAM), also known as CD166, has been identified as the CD6 ligand [8,9].
T28 2891-3026 Sentence denotes ALCAM interaction with CD6 stabilizes the formation of the immune synapse between the lymphocytes and the antigen-presenting cells [5].
T29 3027-3202 Sentence denotes Itolizumab is a humanized monoclonal antibody developed at the Center of Molecular Immunology, in Cuba, that recognizes a region in the distal domain of the human CD6 [10,11].
T30 3203-3386 Sentence denotes The antibody reduces the expression of the intracellular proteins involved in activation and inhibits the proliferation of T cells, even in the presence of the ALCAM and IL-2 [10–12].
T31 3387-3518 Sentence denotes The effect is associated with the reduction of the secretion of pro-inflammatory cytokines including IFN-γ, IL-6 and TNF-α [13,14].
T32 3519-3630 Sentence denotes The antibody has demonstrated to be safe and efficacious in patients with moderate to severe psoriasis [15,16].
T33 3631-3822 Sentence denotes Studies from blood and tissue samples from patients with severe psoriasis showed that itolizumab reduces the proliferation of T cells and serum concentration of IL-6, TNF-α and IFN-γ [13–16].
T34 3823-3907 Sentence denotes A significant reduction of the inflammatory pattern was also observed in the tissue.
T35 3908-4157 Sentence denotes On account of its well proven effect on T-cell activation and proinflammatory cytokines production, itolizumab was included as part of a Cuban expanded access protocol in critical, severe and moderate COVID-19 patients with high risk of aggravation.
T36 4158-4305 Sentence denotes The study will be published soon (manuscript accepted) and here we describe in detail the outcome of three initial patients receiving the antibody.
T37 4307-4324 Sentence denotes Cases description
T38 4325-4335 Sentence denotes Patient 1:
T39 4336-4547 Sentence denotes A 53-year old woman with a personal history of essential hypertension and Type 2 diabetes mellitus presented with symptoms of polypnea of more than 40 rpm, use of respiratory ancillary musculature and dry cough.
T40 4548-4612 Sentence denotes She arrived from a foreign country where COVID-19 was spreading.
T41 4613-4744 Sentence denotes Symptoms started on 23 March and COVID-19 was diagnosed on 26 March on the basis of positive real time PCR (RT-PCR) for SARS-CoV-2.
T42 4745-4901 Sentence denotes Initial gasometry showed moderate hypoxemia and respiratory alkalosis with a partial pressure of oxygen/fraction of inspired oxygen (PO2/FiO2) ratio of 191.
T43 4902-4963 Sentence denotes Chest x-rays showed interstitial lesions in both lung fields.
T44 4964-5057 Sentence denotes She started therapy with lopinavir/ritonavir, chloroquine, recombinant IFN α-2b and rocephin.
T45 5058-5211 Sentence denotes In spite of treatment, the illness subsequently progressed to hypoxemic respiratory failure warranting the initiation of invasive mechanical ventilation.
T46 5212-5396 Sentence denotes At day 13 of her admission in the ICU, she showed radiologic worsening of the interstitial multifocal pneumonia, with elevation of ALP, LDH, erythrocyte sedimentation rate and D-dimer.
T47 5397-5452 Sentence denotes Physicians administered itolizumab at a dose of 200 mg.
T48 5453-5581 Sentence denotes After 48 h of the first itolizumab dose, PO2/FiO2 improved and there were evidences of radiological improvement (Figure 1A & B).
T49 5582-5688 Sentence denotes Patient was extubated after the first dose of the antibody and her status changed from critical to severe.
T50 5689-5772 Sentence denotes She received a second dose of the antibody (200 mg), 48 h after the first infusion.
T51 5773-5879 Sentence denotes 3 days after the first administration, patient was hemodynamically stable and has spontaneous ventilation.
T52 5880-5991 Sentence denotes IL-6 levels were evaluated before itolizumab administration and after 2 and 7 days of the first administration.
T53 5992-6081 Sentence denotes IL-6 levels reduced overtime from 172 pg/ml to 60 pg/ml (day 7) as depicted in Figure 2A.
T54 6082-6153 Sentence denotes IL-1 was evaluated at the same time intervals, but it was undetectable.
T55 6154-6323 Sentence denotes In addition, aspartate amino transferase (AST) concentrations were evaluated at different time points showing a reduction from 43 U/l to 24 U/l after 7 days (Figure 2B).
T56 6324-6380 Sentence denotes No adverse events related with itolizumab were reported.
T57 6381-6390 Sentence denotes Figure 1.
T58 6392-6452 Sentence denotes Radiological images before and after one dose of itolizumab.
T59 6453-6580 Sentence denotes Patient 1 (A) Before itolizumab (D0): diffuse Interstitial-alveolar infiltrate in both lung fields, predominantly in the bases.
T60 6581-6784 Sentence denotes Minor left pleural effusion. (B) After itolizumab (48 h): radiological improvement with decreased diffuse infiltrate and radio-opacity at the top of both lungs and in both lung bases, in less proportion.
T61 6785-6821 Sentence denotes The minor pleural effusion persists.
T62 6822-7094 Sentence denotes Patient 3 (C) Before itolizumab (D0): alveolar interstitial inflammatory infiltrate in both lung fields, predominantly on the right side. (D) After itolizumab (48 h): radiological improvement with significant decrease of the alveolar interstitial infiltrate of both lungs.
T63 7095-7104 Sentence denotes Figure 2.
T64 7106-7147 Sentence denotes Circulating biomarkers in patient's sera.
T65 7148-7256 Sentence denotes IL-6 and AST concentrations kinetics (A & B, respectively) measured in patients during itolizumab treatment.
T66 7257-7267 Sentence denotes Patient 2:
T67 7268-7407 Sentence denotes An 89-year old man with a personal history of chronic ischemic cardiopathy, permanent atrial fibrillation, hypertension and hypothyroidism.
T68 7408-7547 Sentence denotes He has a previous history of alcoholism and several hospital admissions in the last 3 months on account of infectious respiratory diseases.
T69 7548-7650 Sentence denotes He came to the hospital on 2 April after 7 days of shortness of breath, fever, asthenia and dry cough.
T70 7651-7749 Sentence denotes He was in contact with a person who returned from a foreign country, where COVID-19 was extending.
T71 7750-7973 Sentence denotes Physical examination shows signs of respiratory failure characterized by tachycardia, polypnea, intercostal and supraclavicular muscle retraction, high blood pressure, oxygen saturation of 82%, poor diuresis and drowsiness.
T72 7974-8072 Sentence denotes Chest x-rays showed bilateral pulmonary inflammatory infiltrates, predominantly in the right lung.
T73 8073-8225 Sentence denotes Admission ECG showed an atrial fibrillation with rapid ventricular response and the initial gasometry showed severe hypoxemia and respiratory alkalosis.
T74 8226-8373 Sentence denotes Patient also had leukocytosis, altered globular sedimentation rate as well as elevated values of AST, LDH, D-dimer and positive C-reactive protein.
T75 8374-8445 Sentence denotes He was admitted into the ICU requiring invasive mechanical ventilation.
T76 8446-8543 Sentence denotes Treatment with lopinavir–ritonavir, chloroquine, IFN α-2b, meropenem and linezolid was initiated.
T77 8544-8743 Sentence denotes 3 days after his admission into the ICU, itolizumab was prescribed, due to worsening of the bilateral pulmonary infiltrates together with a deterioration of the ventilatory function (PO2/FiO2 = 173).
T78 8744-8882 Sentence denotes After the first antibody infusion, PO2/FiO2 significantly increased (PO2/FiO2 = 320) and there were evidences of radiological improvement.
T79 8883-9053 Sentence denotes 3 days after, patient showed radiological worsening of the left lung, characterized by alveolar hypoventilation and atelectasis; then, a 70% pneumothorax was established.
T80 9054-9166 Sentence denotes Treatment of the pneumothorax with minimal pleurotomy was very demanding and required 3 days for the resolution.
T81 9167-9361 Sentence denotes The patient received a second infusion of the monoclonal antibody 72 h after the first, while a third dose was administered at the discretion of the treating physicians, 2 days after the second.
T82 9362-9458 Sentence denotes In total, patient received three doses of itolizumab (200 mg) without any related adverse event.
T83 9459-9573 Sentence denotes IL-6 levels were evaluated before itolizumab administration and after 2, 4 and 7 days of the first administration.
T84 9574-9730 Sentence denotes IL-6 was extremely high at baseline (623 pg/ml) and even though cytokine levels reduced roughly 50%, the lowest value remained above 300 pg/ml after 7 days.
T85 9731-9767 Sentence denotes IL-6 kinetics is shown in Figure 2A.
T86 9768-9841 Sentence denotes Apart from IL-6, IL-1 was undetectable at this time point of the disease.
T87 9842-9935 Sentence denotes Interesting, in the case of AST, a significant reduction is detecting at day 7 (pretreatment:
T88 9936-9948 Sentence denotes 156 U/l, D7:
T89 9949-9983 Sentence denotes 40 U/l) as is showed in Figure 2B.
T90 9984-10131 Sentence denotes After 10 days of admission into the ICU, patient presented a myocardial dysfunction and shock that required vasoactive support with norepinephrine.
T91 10132-10221 Sentence denotes On day 13, he finally died, on account of a mixed cardiovascular and respiratory failure.
T92 10222-10232 Sentence denotes Patient 3:
T93 10233-10341 Sentence denotes An 81-year old female, who is COVID-19 positive contact was not identified at the moment of hospitalization.
T94 10342-10500 Sentence denotes She started symptoms on 2 April and entered the ICU on 5 April. Patient has a previous history of hypertension, diabetes mellitus, glaucoma and smoking habit.
T95 10501-10561 Sentence denotes She was admitted with frequent cough, wheezing and diarrhea.
T96 10562-10642 Sentence denotes The diagnosis of viral pneumonia by COVID-19 was confirmed by RT-PCR on 7 April.
T97 10643-10761 Sentence denotes Oxygen support at 5 l/min and treatment with ceftriaxone, lopinavir–ritonavir, chloroquine and IFN α-2b was indicated.
T98 10762-10832 Sentence denotes Chest images showed bilateral interstitial infiltration in both lungs.
T99 10833-10938 Sentence denotes Patient condition was classified as severe, although she did not require invasive mechanical ventilation.
T100 10939-11020 Sentence denotes A dose of itolizumab (200 mg) was given the day after her admission into the ICU.
T101 11021-11267 Sentence denotes Two days after the antibody administration, together with the rest of the therapy, there was an improvement of the respiratory distress while the chest image showed a decrease of the alveolar interstitial infiltrate of both lungs (Figure 1C & D).
T102 11268-11343 Sentence denotes Patient left the ICU after a favorable clinical and radiological evolution.
T103 11344-11420 Sentence denotes IL-6 concentration was measured prior and after the antibody administration.
T104 11421-11596 Sentence denotes IL-6 level at baseline was lower than in previous cases (30 pg/ml), but also decreased 48 h and 168 h after itolizumab infusion, in parallel with patient recovery (Figure 2A).
T105 11597-11679 Sentence denotes IL-1 and TNF-α were untraceable before and 48 h after the antibody administration.
T106 11680-11788 Sentence denotes Regarding to AST concentration, the values were in the normal range during the treatment period (Figure 2B).
T107 11790-11809 Sentence denotes Materials & methods
T108 11810-12054 Sentence denotes Three patients with diagnosis of COVID-19 classified as critically ill (two) and severely ill (one) were included in an expanded access trial to receive itolizumab in addition to standard treatment (http://rpcec.sld.cu/trials/RPCEC00000311-En).
T109 12055-12189 Sentence denotes The study was approved by a central ethical review board, created especially for COVID-19 and by the Cuban Regulatory Agency (CECMED).
T110 12190-12264 Sentence denotes Before the treatment, informed consent was obtained from enrolled patient.
T111 12265-12374 Sentence denotes Laboratory results included blood routine, leucocyte subsets and blood biochemical parameters were collected.
T112 12375-12655 Sentence denotes The level of inflammatory cytokines was measured using human validated commercially available kit from R&D Systems (MN, USA): human IL-6 Quantikine ELISA Kit (Cat# S6050), human IL-1 beta/IL-1F2 Quantikine ELISA Kit (Cat# SLB50) and human TNF-α Quantikine ELISA Kit (Cat# STA00D).
T113 12656-12749 Sentence denotes In the case of IL-6, the normal range of this cytokine in sera is between 0 and 7 pg/ml [17].
T114 12750-12850 Sentence denotes We used intra-assay precision and inter-assay precision methods to evaluate precision in this study.
T115 12851-13000 Sentence denotes For intra-assay precision (precision within an assay), three samples of known concentration were tested on one plate to assess intra-assay precision.
T116 13001-13155 Sentence denotes For inter-assay precision (precision between assays), three samples of known concentration were tested in separate assays to assess inter-assay precision.
T117 13157-13167 Sentence denotes Discussion
T118 13168-13230 Sentence denotes CRS is characterized by high levels of inflammatory cytokines.
T119 13231-13313 Sentence denotes Among them, IL-6 is considered a major mediator of this hyperinflammation [18,19].
T120 13314-13422 Sentence denotes Most of the COVID-19 patients-related papers showed the CRS as one of the main hallmark of the disease [20].
T121 13423-13492 Sentence denotes Additionally, IL-6 levels predict severity in COVID-19 patients [21].
T122 13493-13595 Sentence denotes There is high heterogeneity of IL-6 values among papers for classifying severe and nonsevere patients.
T123 13596-13743 Sentence denotes In a large meta-analysis of 52 manuscripts, Elshazli and coworkers found that the IL-6 level associated with COVID-19 severity was 22.9 pg/ml [22].
T124 13744-13907 Sentence denotes In a series of patients treated with itolizumab a cutoff of 28 pg/ml discriminates severe patients from nonsevere (manuscript just accepted in Immunity and Aging).
T125 13908-13997 Sentence denotes In the present study, the IL-6 concentration of the three patients was above this cutoff.
T126 13998-14096 Sentence denotes It confirms the classification of these patients as severe and that the CRS is probably occurring.
T127 14097-14208 Sentence denotes Several anticytokine therapies have been tried for treating the hyperinflammatory phase of COVID-19 [20,23–25].
T128 14209-14336 Sentence denotes Here, we report the use of a well-known anti-inflammatory antibody targeting CD6 to treat the CRS arising in COVID-19 patients.
T129 14337-14568 Sentence denotes Using an anti-CD6 antibody could reduce the concentration of several pro-inflammatory cytokines, including IL-6, IFN-γ, TNF-α and IL-17, among others, representing an advantage as compared with single-cytokine targeting antibodies.
T130 14569-14694 Sentence denotes The antibody would not exacerbate lymphopenia since it does not induce complement or antibody dependent cytotoxicity [10,11].
T131 14695-14812 Sentence denotes These three SARS-CoV2 patients developed severe respiratory distress together with multifocal interstitial pneumonia.
T132 14813-14917 Sentence denotes Two patients required invasive mechanical ventilation while the third patient only needed oxygen supply.
T133 14918-15103 Sentence denotes They all received the anti-CD6 antibody itolizumab in combination with other drugs incorporated into the Cuban national protocol, including lopinavir/ritonavir, chloroquine and IFNα-2b.
T134 15104-15262 Sentence denotes Regarding to laboratory parameters, AST is strongly associated with mortality risk compared with other parameters, reflecting liver and kidney injury [26,27].
T135 15263-15431 Sentence denotes In our cases, critically ill patients showed a significant reduction of AST concentration after the treatment suggesting an improvement in the function of these organs.
T136 15432-15523 Sentence denotes Itolizumab was very safe and did not seem to exacerbate opportunistic secondary infections.
T137 15524-15649 Sentence denotes Unfortunately, we did no measure neither the frequency nor the total amount of circulating T cells in these initial patients.
T138 15650-15747 Sentence denotes The impact of itolizumab on circulating T cells are being implementing in new recruited patients.
T139 15748-15929 Sentence denotes Our preliminary findings support that IL-6 levels correlated with the severity of the disease and that the antibody was capable of reducing IL-6 concentration in all three subjects.
T140 15930-16009 Sentence denotes One patient died after subsequent respiratory and cardiovascular complications.
T141 16010-16114 Sentence denotes In this particular case, IL-6 concentration was extremely elevated at the moment of itolizumab infusion.
T142 16115-16232 Sentence denotes Although, the levels of IL-6 decreased during treatment, the values at 7 days kept still very high (above 300 pg/ml).
T143 16233-16313 Sentence denotes There was a transient improvement of respiratory function but it was not enough.
T144 16314-16527 Sentence denotes Presumably, the consequences of the hyperinflammatory syndrome (thrombosis, alveolar damage and severe tissue hypoxia) were irreversible at the moment of treatment and patient died as consequence of these factors.
T145 16529-16539 Sentence denotes Conclusion
T146 16540-16647 Sentence denotes In summary, in these severe and critically ill patients, itolizumab was able to reduce IL-6 concentrations.
T147 16648-16709 Sentence denotes Notably, itolizumab-related adverse events were not reported.
T148 16710-16811 Sentence denotes Patients with baseline IL-6 levels below 200 pg/ml, showed prompt clinical and radiological recovery.
T149 16812-17005 Sentence denotes We anticipate that the timely use of this anti-inflammatory antibody in combination with the appropriate antiviral and anticoagulant therapy could reduce the mortality associated with COVID-19.
T150 17006-17068 Sentence denotes The analysis of the complete-series will be published shortly.
T151 17069-17083 Sentence denotes Summary points
T152 17084-17196 Sentence denotes Inflammatory cytokine-release syndrome is associated with the progression of the coronavirus disease (COVID-19).
T153 17197-17280 Sentence denotes No current therapy has proven effective for the management of this syndrome so far.
T154 17281-17439 Sentence denotes Itolizumab is a humanized monoclonal antibody that recognizes human CD6 and its effect is associated with the reduction of pro-inflammatory cytokines release.
T155 17440-17562 Sentence denotes We present three COVID-19 cases who developed severe respiratory distress together with multifocal interstitial pneumonia.
T156 17563-17639 Sentence denotes The patients were treated with itolizumab combined with antiviral therapies.
T157 17640-17722 Sentence denotes Itolizumab reduced circulating IL-6 concentrations in the three COVID-19 patients.
T158 17723-17815 Sentence denotes Two patients showed rapid ventilatory and radiological improvement and were fully recovered.
T159 17816-17868 Sentence denotes Itolizumab-related adverse events were not reported.
T160 17869-18065 Sentence denotes These cases show that the timely use of this anti-inflammatory antibody in combination with the appropriate antiviral and anticoagulant therapy could reduce the mortality associated with COVID-19.
T161 18067-18087 Sentence denotes Author contributions
T162 18088-18125 Sentence denotes Study design and data interpretation:
T163 18126-18396 Sentence denotes G Lorenzo, M Cepeda, M Ramos, D Saavedra, Z Mazorra, K Leon and T Crombet; clinical investigators (recruited and treated patients): LM Filgueira, JB Cervantes, OA Lovelle, C Herrera, C Figueredo, JA Caballero, N Sánchez, J Berrio, A Caballero; immunological assessments:
T164 18397-18476 Sentence denotes D Saavedra, AL Añe-Kouri, Z Mazorra; writing and or/revision of the manuscript:
T165 18477-18503 Sentence denotes T Crombet and A Caballero.
T166 18505-18520 Sentence denotes Acknowledgments
T167 18521-18652 Sentence denotes We are extremely grateful to all ICU physicians, nurses and general staff working with severe and critically ill COVID-19 patients.
T168 18654-18696 Sentence denotes Financial & competing interests disclosure
T169 18697-18908 Sentence denotes Seven authors (G Lorenzo, M Cepeda, M Ramos, D Saavedra, Z Mazorra, K Leon and T Crombet) currently work for the Center of Molecular Immunology, the institution that generated and originally patented itolizumab.
T170 18909-19041 Sentence denotes The remaining authors do not have any commercial or financial relationships that could be taken as a potential conflict of interest.
T171 19042-19290 Sentence denotes The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
T172 19291-19363 Sentence denotes No writing assistance was utilized in the production of this manuscript.
T173 19365-19392 Sentence denotes Ethical conduct of research
T174 19393-19542 Sentence denotes The authors state that they have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.
T175 19543-19677 Sentence denotes The study was approved by a central ethical review board, created especially for COVID-19 and by the Cuban Regulatory Agency (CECMED).
T176 19678-19752 Sentence denotes Before the treatment, informed consent was obtained from enrolled patient.
T177 19754-19776 Sentence denotes Data sharing statement
T178 19777-19888 Sentence denotes The authors certify that this manuscript reports original clinical trial data on three patients, RPCEC00000311.
T179 19889-20076 Sentence denotes Individual participant data that underlies the results reported in the article, after de-identification (text, tables, figures and supplement) are available along with the study protocol.
T180 20077-20192 Sentence denotes The data will be available 9 months after article publication and will end 36 months following article publication.
T181 20193-20405 Sentence denotes The information will be shared with investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose and for individual participant data meta-analysis.
T182 20406-20479 Sentence denotes Proposals may be submitted up to 36 months following article publication.
T183 20480-20608 Sentence denotes After this date the data will be available in our data warehouse but without investigator support other than deposited metadata.
T184 20609-20729 Sentence denotes Information regarding submitting proposal and accessing data may be found at http://rpcec.sld.cu/trials/RPCEC00000311-En